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generalized cytokine responses to stress may be modified by specific nutrients. The focus of the Army's current research program is in this direction, examining the effect of nutrition on sustainment or enhancement of immune status in healthy individuals.

Immune Suppression and Inflammatory Responses to Operational Stressors

A current objective of Army operational medicine research is to identify the effect of operational stressors and other battlefield hazards on soldiers' immunological and/or inflammatory host defenses. Problems must be defined in relevant models of operational stress and in terms of actual disease susceptibility (Kusnecov and Rabin, 1994); research to develop nutritional countermeasures is appropriate after problems have been clearly identified. Stressors that are being investigated in military studies include chronic anxiety (referred to in the remainder of this chapter as "psychological stress"), inadequate restorative sleep, physical exertion, inadequate energy intake, industrial toxicological hazards, and mechanical/physical stresses (e.g., blast and laser injuries).

Psychological stressors are the best documented in terms of stress effects on immunological impairment, and an entire interdisciplinary field of psychoneuroimmunology is founded on studies linking the immune and central nervous systems (Ader and Cohen, 1993). The Department of Medical Neurosciences at the Walter Reed Army Institute of Research (WRAIR) has investigated acute and chronic rodent stress models actively (e.g., footshock in mice, learned helplessness in defeat-conditioned hamsters2), helping to define mechanisms of stress effects on the brain (Huhman et al., 1991, 1992). Footshock as well as chronic anxiety stress reliably suppresses T-cell proliferation and lymphocyte IL-2 production in rodents (hardy et al., 1990). While adrenocorticoids suppress potentially maladaptive overresponses of immune function (Kapcala et al., 1995), LTC Ned Bernton has demonstrated that their effect is counterbalanced by other factors, such as dehydroepiandrosterone (DHEA) and some of the lactogens, that may reverse corticotropin-releasing factor-mediated decrements in immune function (Bernton et al., 1988, 1992; Rassnick et al., 1994). Studies of combat veterans with posttraumatic stress disorder suggest that, even with adrenal adaptation, anxiety may increase glucocorticoid receptors on lymphocytes (Yehuda et al., 1990, 1991); thus, circulating levels of cortisol may be low and still significantly affect immunogenic tissues (Dhabhar et al., 1995). These basic studies help to explain and verify observed links between psychological stress and illness (Cohen et al., 1991; Lee et al., 1995; Rubin et al., 1970, 1971),


A model of stress in which the male hamster, accustomed to attacking unfamiliar hamsters introduced into his cage, is repeatedly defeated by larger, more aggressive intruders until his normal territorial aggression is replaced by defensive behavior and flight.

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