Immune Response: Wildland Firefighter Health and Safety Recommendations of the April 1999 Conference, 9951-2841-MTDC

Thermal burn injuries of a large body surface area induce a systemic inflammatory response that also is associated with immune dysfunction (Lyons et al. 1997; O’Sullivan et al. 1995). The immunological effect of smaller thermal burns has not been extensively studied. There are indications that tissue and systemic antioxidant concentrations decrease after smaller thermal burns (Rock et al. 1997), which could impact immune function. Furthermore, burn injury predisposes burn patients to infections, poor wound healing, and increased nutrient requirements. Nutritional strategies to support the health of the burn patient requires diets of highly bioavailable protein, containing specific components that may aid in maintaining or strengthening the immune system.

Chemicals in smoke that wildland firefighters may be exposed to can affect the immune system. Smoke exposure has been a recognized health issue for fire management for many years (Liu et al. 1992). A few studies in the 1970’s hinted that smoke exposure contributed to fatigue and injuries. The main inhalation hazards are carbon monoxides, aldehydes, benzene, acrolein, and respirable particulate matter (Materna et al. 1992). Firefighters occasionally report illness from exposure to smoke. Links between smoke exposure and morbidity are not currently understood.

Starvation has also been shown to affect the immune system. For example, starvation causes involution of the thymus (primary immune organ), it reduces cytokine production, reduces the numbers of T-lymphocytes, and increases incidence of infection. Zaman et al. (1997) studied malnutrition in children from Bangladesh and found that modest malnutrition reduced immunocompetence and increased the incidence of upper respiratory tract infections. Results indicated that children that were anergic to DTH (delayed type-skin hypersensitivity) had a 20% higher risk of developing an upper respiratory tract infection.

Nutritional deficiencies or suboptimal nutrient levels can be the result of inadequate intake, decreased absorption, or increased utilization of nutrients. Furthermore, many nutrients are required for optimal functioning of the immune system. Therefore, when nutrients are depleted or when nutrients have been suboptimal, immunological impacts place an individual at risk of infection. The inpacts include:

Impairing the immune cells from recognizing foreign stimuli
Altering the proliferative responses of the immune cells
Impairing the antigen presentation
Reducing the killing capacity of the immune cells
Changing the membranes or cooperative interaction between the various cell types involved in the immune system.

Once an individual has become infected, increased nutrient utilization or malabsorption occurs, which further increases the individual’s nutritional requirements (Figure 4). Medications and antibiotics may disrupt gastrointestinal flora, exacerbating diarrhea (decreasing absorption) and compromising the nutritional state. Nutritional supplementation can influence nutritional status and ultimately impact immune function. There are also many interactions between nutritional status and immune function in this cycle.

The effect of infection on nutritional status is characterized by wasting of peripheral tissues, particularly lean body mass (muscle). This seems to be the result of cytokine-mediated responses designed to support the immune system and fight against infection. Paradoxically, these mediators, when secreted in excessive or inappropriate amounts, have been associated with morbidity and mortality in a wide range of conditions (such as rheumatoid arthritis, inflammatory bowel disease, and sepsis). Nutrients (vitamins and minerals) are used as substrate and co-factors for immune cells. Once an infection takes place, immune cells have a higher requirement for nutrients (see Figure 4 outlining the concept and interactions). Furthermore, upon infection, particularly of the gastrointestinal tract, there is mucosal damage and the microflora of the gut changes. The absorptive capacity of the small intestine decreases, leading to malabsorption. The mucosal and microflora changes can also be influenced by antibiotics and medications as well as by decreases in the effectiveness of nutrient absorption. This damage may cause diarrhea, further compromising the nutritional status and suppressing immune function, which further compromises the body’s ability to fight the infection. Nutrient supplementation can prevent malnutrition and provide the essential factors immune cells need to function optimally. An infection may also cause increased utilization of nutrients, influencing nutritional requirements.

To demonstrate the importance of an optimal level of nutrients, Chandra reported (1996) that inadequate nutrient consumption hampers the immune system’s ability to fight an infection. He fed mice approximately 40% of the nutrient requirement for 3 weeks, and then challenged the mice with L. monocytogenes intraperitoneally. These mice had a survival rate approximately half that of mice fed an adequate level of nutrients (Figure 5). Nutrition impacts the immune system by providing essential components for immune cells to function properly. Nutrition presents a possible strategy to combat immune suppression induced by stress. Adequate nutrients will provide for optimal immune function. Chandra stated, “The era of nutritional manipulation of the immune system has finally dawned and it brings with it the promise of using diet and nutrition as innovative powerful tools to reduce illness and death caused by infection” (Chandra 1996, p. 1,430).

Graph showing results from mice feedings.

Figure 5—Eight-week-old C57Bl/6 X DBA/2F hybrid male
mice were fed approximately 40% of the nutrient requirement
for 3 weeks and divided into two groups (formula enriched with
nutrients known to simulate the immune responses-100% group
and the 40% formula group). After 2 weeks, the mice were
challenged with 4 x 104 L. monocytogenes intraperitoneally. Survival
was noted (Chandra 1996).

Nutrient supplementation can also affect immune function and counteract the stress-induced immune changes. Appendix A contains a summary table of many nutrients and their influence on immune function. Supplementation as a means to minimize or prevent immune changes and protect individuals who are undergoing physical stress has been studied to a limited extent. There are suggestions that nutrients such as vitamin C play a role in immune function and may prevent immune suppression in physically stressed individuals. Vitamin C is found in high concentrations in leukocytes and its concentration decreases rapidly during infections, which suggests that vitamin C is an important factor in immune function (Thomas and Holt 1978). Peters et al. (1993) supplemented the diets of ultramarathon runners for 21 days before an ultramarathon with either 600 mg vitamin C/day or a placebo. They then established the incidence of symptoms of upper-respiratory-tract infection during the 14 days after the race. Sixty-eight percent of the runners who consumed the placebo reported upper respiratory tract infections compared with 33 percent of those who consumed the C vitamin. It has also been shown that physical activity raises oxygen demand severalfold, increasing the formation of oxygen radical species (Giuliani and Cesaro 1997; Alessio 1993). As oxygen radical species are formed, they adversely affect immune function (Aruoma 1994). Theoretically, providing antioxidants in sufficient amounts during exercise-induced oxidative stress may prevent immune dysregulation (Witt et al. 1992). Several reviews on the importance of dietary components, such as antioxidants, and their influence on multiple aspects of the immune response and immune system have been published (Corman 1985; Chandra 1990).

Shepard and Shek (1995) postulated that athletes and other health-conscious persons may participate or adopt unusual nutrition programs that may influence their overall nutritional status and ultimately impact immune function. Furthermore, prolonged or chronic stress and exercise may deplete muscle glycogen or other nutrients and lead to competition with immune cells.

Few opportunities have existed to conduct well-controlled field research to study the effect of stress on immunological responses. Nutrition is an important factor that can be manipulated to minimize immune dysregulation during stressful situations. For example, it is not uncommon to observe diminished immune response (anergy) to DTH in individuals with severe malnutrition. The influence of mild malnutrition on immune regulation and an understanding of specific levels of nutrients for optimal nutrition remain to be investigated.

Nutritional inadequacies result in immune dysregulation and can profoundly influence susceptibility to infection. Cells of the immune system require a variety of nutrients for proper function. Furthermore, nutrients play a vital role in enzyme synthesis and activity required for normal immune function (many kinases and transferases require zinc). Garcia-Tamayo et al. (1996) found zinc treatment to chronically stressed mice ameliorated the metabolic and immunologic effects of chronic stress.

Ross Products Division/Abbott Laboratories has investigated potential benefits of nutrient supplementation and nutritional strategies to minimize immunologic changes in a variety of conditions. The difficulty has been in identifying models or clinical scenarios where immunologic dysregulation occurs and in having an opportunity to intervene with nutrients. One promising situation we have evaluated has been United States military training. The military stresses (such as carrying heavy packs and equipment, strenuous physical exertion, exposure to extreme temperatures, and psychological stress) seem to be similar to those experienced by wildland firefighters. A field study is summarized below, describing our findings.

Historically, soldiers during military deployment and wartime refugees have demonstrated an increased incidence of infectious diseases. Furthermore, soldiers in military training have also incurred higher than expected infectious disease outbreaks, pointing toward an underlying susceptibility. The U.S. Army Special Forces Assessment and Selection Course (SFAS) is highly demanding, both physically and emotionally (21 days duration). Fairbrother et al. 1995 documented a negative energy balance (1,379 kcals/day) in soldiers who participated in the course; however, there were no significant clinical manifestations of vitamin and/or mineral deficiencies. One observation from that study was a reduced lymphocyte proliferation response (reduced 23 percent on average) to mitogen stimulation . This observation suggested that multistressors (negative energy balance, sleep deprivation, physical activity, and psychological stress) may have negative effects on immune function and the ability of lymphocytes to combat infections. For example, Bernton et al. (1995) found that during U.S. Army Ranger training, DTH skin anergy increased over time and those that did respond had a decreased response (Table 4).Historically, soldiers during military deployment and wartime refugees have demonstrated an increased incidence of infectious diseases. Furthermore, soldiers in military training have also incurred higher than expected infectious disease outbreaks, pointing toward an underlying susceptibility. The U.S. Army Special Forces Assessment and Selection Course (SFAS) is highly demanding, both physically and emotionally (21 days duration). Fairbrother et al. 1995 documented a negative energy balance (1,379 kcals/day) in soldiers who participated in the course; however, there were no significant clinical manifestations of vitamin and/or mineral deficiencies. One observation from that study was a reduced lymphocyte proliferation response (reduced 23 percent on average) to mitogen stimulation . This observation suggested that multistressors (negative energy balance, sleep deprivation, physical activity, and psychological stress) may have negative effects on immune function and the ability of lymphocytes to combat infections. For example, Bernton et al. (1995) found that during U.S. Army Ranger training, DTH skin anergy increased over time and those that did respond had a decreased response (Table 4).

Table 4—Summary of Delayed Type-Skin Hypersensitivity (DTH) skin test from Ranger training (Bernton et al. 1996)

The SFAS scenario provided a unique population because the soldiers have similar environmental factors (including diet and physical stress), suppressed immune function, and higher rates of infection than nonstressed soldiers. Nutrition intervention allowed for an evaluation of nutritional supplementation on immune function (suppressed in previous studies). Furthermore, military training scenarios permitted the evaluation of a large number of subjects in a short period.

Two hundred soldiers participating in a Special Forces Assessment and Selection School (SFAS) course conducted by the U.S. Army John F. Kennedy Special Warfare Center and School, Fort Bragg, North Carolina, volunteered to participate in this prospective, randomized, blinded, placebo-controlled study. The test group (n = 100 soldiers) was designated to consume their regular diet consisting mainly of meals ready-to-eat (MRE) plus a novel ready-to feed treatment product (8 oz two times per day) containing antioxidants, minerals, and a structured lipid (from long- and medium-chain fatty acids), and indigestible carbohydrates. The control group (100 soldiers) consumed a ready-to-feed product of similar taste and appearance containing similar amounts of macronutrients and energy. Dietary intake, body weight change, and immune function were measured before and after the physically and psychologically demanding 21-day training course.

In the treatment group, 50 of 100 soldiers completed the course compared to 57 of 100 from the control group. Soldiers dropped from the course primarily for administrative or voluntary reasons. Rates were similar to previous courses in previous years. There were no differences between drop rates and reported intolerance to either product. Subjects lost approximately 6.4 pounds in 3 weeks. Combining the dietary intake with the weight loss data, it was estimated that soldiers had an energy expenditure of 5,040 kcals per day.

Week of training	Subjects (n)	Total induration	% Anergic

0	40	17.9±	0
6	40	10.5±1.0	2
8	26	6.3±1.0	15

The in vivo measurement of overall cellular immune function, delayed type-skin hypersensitivity (DTH) at exit (total induration), suggested that subjects consuming the treatment product had a greater response (P = 0.07 that the difference was due to chance). Similarly, fewer subjects in the treatment group were DTH anergic (18% compared to 39% in the control group) to the skin test, suggesting a lower risk for infections in the treatment group. The percentage of soldiers in the control group who were anergic was consistent with previous studies in SFAS. By contrast, there was a trend toward increased lymphocyte responsiveness to mitogen stimulation from soldiers fed the treatment product. Several changes were noted in lymphocyte subsets during the course of the study. The pattern of change in white blood cells, lymphocyte numbers, and subsets was consistent with increased risk of infection within SFAS. The treatment product attenuated some of the changes. Cell profile changes in the treatment group also seemed to indicate that neutrophils may have been migrating to the target or affected tissues (skin or lungs) rather than circulating in the blood. Maintenance of lymphocyte populations such as cytotoxic/suppressor, Th1 lymphocytes, and neutrophil phagocytosis were found in the group fed the treatment formula. Overall, the treatment formula appeared to minimize or attenuate the immunologic changes associated with SFAS training (strenuous physical and emotional stress).

A similar study was conducted during the 62-day Ranger training. We formulated a novel nutrition bar containing a nutrient profile similar to that of the ready-to-drink formula used in the SFAS study. The treatment bar lessened some of the immunological changes and appeared to help maintain weight better than the placebo product.

Conclusions and Future Focus

The immune system is an intricate and highly regulated network of cells, tissues, and molecules that aid in warding off infections and disease. Although the effectiveness of the immune response can be influenced by a number of stressors, specialized nutrition can minimize or prevent immune dysregulation.

No studies have been conducted to evaluate immune function in wildland firefighters. It seems logical that they would experience some level of immune suppression from the stresses to which they are exposed. It would be important to establish whether these individuals have increased risk of infection compared to nonstressed firefighters. If there is an increased risk or rate of infection, it would be valuable to study strategies (such as nutritional supplementation) that might influence the immune system under these conditions. Specific nutritional formulations tested in military training where the physical and psychological stresses may be similar to those of wildland firefighting may be of value to firefighters.

Appendix A

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Nutrient	Effect on Immune Function
Energy	Caloric deprivation associated with decreased antibody response, decreased anti-DNA antibodies, decreased/increased thymocyte proliferation in response to exogenous IL-2, and decreased/increased IL-2 production in response to stimulation with mitogens.
Protein	Deficiency affects all components of the immune system including depressed cell-mediated immunity, delayed hypersensitivity skin test, B-lymphocyte function, macrophages, neutrophils, and complement.
Arginine	Deficiency compromises cellular immune mechanisms, particularly T-lymphocyte function. Supplemental arginine increases thymic size and number of T lymphocytes, suppresses tumor growth, and decreases incidence of infection.
Glutamine	Energy substrate for macrophages and T lymphocytes.
Lipids n-6 fatty acids	Linoleic acid deficiency causes dermatitis and impaired wound healing. Prostaglandin E 2 (a metabolite of linoleic acid) may depress cytostatic functions, lymphocyte mitogenesis, production of lymphokines, cytolysis, facilitate tumor growth, and prolong allograft survival
n-3 fatty acids	n-3 fatty acid deficiency may induce neurological deficits, dermatitis and immunological changes; increased levels improve cell-mediated immune responses and opsonic indices, increase splenic weight, and inhibit production of immunosuppressive dienoic prostaglandins.
Zinc	Deficiency produces increased susceptibility to infection, depressed circulating thymic hormone, altered complement function, marked atrophy of the thymus; reduction in leukocytes (especially Tlymphocyte percentage) and antibody-mediated, cell-mediated, phagocytosis as well as delayed hypersensitivity skin test responses. Excessive intake causes specific defects in the function of T lymphocytes and granulocytes.
Iron	Deficiency produces impaired bacterial killing ability of phagocytic cells, impaired lymphocyte response to mitogen stimulation, and decreased rosette-forming T lymphocytes.
Selenium	Deficiency may impair antibody production and the bacteriocidal activity of neutrophils; slight excess may reduce susceptibility to infection and enhance antibody production and splenic plaque cell formation (immunostimulatory actions may be potentiated by vitamin E).
Manganese	Required for normal antibody synthesis and/or secretion; excess inhibits antibody formation and chemotaxis, and increases susceptibility to pneumococcal infection.
Magnesium	Deficiency can cause thymic hyperplasia, impair cell-mediated immunologic responsiveness, decrease serum IgG, IgG2, IgA levels, and reduce hemagglutinin responses.
Copper	Deficiency associated with increased rate of infections, depressed immune system and microbicidal activity of granulocytes, impaired antibody response, and depressed thymic hormone.
Vitamin A	Deficiency may increase susceptibility to infection, cause atrophy of lymphoid tissues, decrease lymphocyte counts, suppress antibody production, reduce in vitro lymphocyte response to mitogens, suppress delayed dermal hypersensitivity, reduce mobilization of peripheral macrophages, and increase the serum concentration of hemolytic complement.
ß-Carotene	Modest doses of ß-carotene enhance immune responses.
Vitamin B6	Deficiency depresses antibody production and delayed dermal hypersensitivity, and may cause atrophy of lymphoid tissues, decreased lymphocyte counts, and diminished inflammatory response.
Vitamin C	Deficiency may increase susceptibility to infection, reduce the percentage of T lymphocytes, prolong allograft survival, suppress the recall mechanism of delayed dermal hypersensitivity, impair the function of neutrophils and macrophages, reduce thymic humoral factors, and enhance complement concentration.
Vitamin D	Deficiency causes anergy in the delayed hypersensitivity skin test.
Vitamin E	Deficiency depresses immunological responses to antigens, lymphocytic proliferative responses, delayed dermal hypersensitivity, and general resistance. Slight excess enhances antibody responses to vaccines (effect is compounded by selenium deficiency), delayed type skin hypersensitivity, clearance of particulate matter by the reticuloendothelial system, and general resistance. Supplements containing vitamin E have shown enhanced immune function. Furthermore, supplementing the diets of elderly subjects minimizes the age-induced immune suppression
Folate	Deficiency may depress lymphocyte counts, antibody response to immunization, in vitro lymphocyte responses, and delayed dermal hypersensitivity.
Thiamine	Deficiency may depress splenic plaque-forming cell response to immunization.
Riboflavin	Deficiency generally depresses primary response of antibody production after immunization.
Pantothenic acid	Deficiency generally depresses antibody response to immunization and may depress splenic plaqueforming cell response to immunization.
Biotin	Deficiency may depress antibody response to immunization and splenic plaque-forming cell response to immunization.
Vitamin B12	Deficiency may depress in vitro lymphocyte responses and neutrophil functions.
Multinutrients	Supplementation with multinutrient preparations have decreased incidence of nutrient deficiency, infection, and attenuated immune suppression/dysregulation.
Herbals & others	Echinacea, Ginseng, Gingko Biloba, St. John’s Wort, Mother’s Wort, Dehydroepiandrosterone (DHEA), Melatonin, Phytonutrients, soy extracts, undenatured whey protein, lactoferrin, polyclonal antibodies from milk or eggs. A variety of compounds have been found either in uncontrolled clinical studies, testimonials, animal studies, or in vitro studies to indicate some immunologic potential.