Immunological mechanisms in stress-induced immunomodulation

IMMUNOLOGICAL MECHANISMS IN STRESS-INDUCED IMMUNOMODULATION Berkenbosch F, Derijk R, Persoons J.H.A. & Kraal G., Departments of Pharmacology and Histology, Medical Faculty, Free University, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Male Wistar rats were exposed to unescapable footshocks (50 Hz, 0.5 mA, 4 s, 4 shocks/min) for a period of 20 min. Splenic cells were isolated directly after foctshock egposure to test their capacity to proliferate in vitro in response to ",hemitogen concanavalin A. Splenic T-cells of rats exposed to footshock~ showed a markedly reduced mitogen response as compared to that of nons~ressed home-cage controls. This difference in mitogen response appeared not to be due to stress-iuduced changes in cell composition of the isolated splenic cells as revealed by Fluorescence Activated Cell Sorter (FACS) analysis of isolated splenic cell using antibcdies specific for T- and B-cell subsets. Subsequently, we tested whether footshock-induced effects could be due to functional changes of im:nune and/or accessory cells. To that end, we studied the effects of footshoek stress on circulating levels of lnterleukin-I b e t (It,-1) concentrations induced by intravenous injection of bacterial eudotoxin (LPS). This parameter was selected, as this cytokine has been shown to coordinate the host response to infection which includes immunological (T-cell proliferation), behavioral (inactivity, sleepiness, appetite) and physiological (fever) responses. 1L-1 plasma concentrations were measured by using a newly developed IL-1 radioimmunoassay (RIA) specific for detection of rat-IL-1 beta. The plasma IL-1 concentrations detected by our RIA predominantly originates from macrophages, since macrophage-depletlon induced by injecting rats with liposomes encapsulated with the toxic drug dichloromethylene diphosphonate completely abrogates the plasma IL-1 response to LPS. Footshock exposure prior to LPS injection resulted in a markedly blunted plasma IL-1 response to eudotoxin. Tbese data suggest that at least one level at which footshock stress may influence immune function is by altering the functional capacity of macrophages to release immunoregulatory signals such as ¢,ytokines.

ANTIGEN-SPECIFIC TACHYCARDIA AND HYPOTHERMIA IN ANAPHYLAXIS Huan-Yho Lei, Shur-Hwa Lee and Shin-shing Leir Department of Microbiology, College of Medicine, National Cheng Kun8 University, Tainan, Taiwan, R.0.C. Recently, a novel antigen-specific hypersensitivity which does not fit into traditional classification of hypersensitivity was repotted (J.I. 143,432, 1989). This type of hypersensitivity was elicited within 1 h after challenge, it could be transferred by small molecular T-cell products or heat-resistant immune sera, and was called early-type hypersensitivity (ETH). The response pattern of ETH seems to inversely related to DTH and lasted longer. In this study, we examined the immunophysiological response when the antigen was given intravenously onto the antigen-sensitized mice. The mice would develop anaphylactic symptoms such as lethargy, tachypneic, myoclonic jerk and sometime would die within 1 h. Either tachycardia or hypothermia would be induced antigen specifically. The response of tachycardia that evolved within 1 min. and sustained for I h can not be inhibited by either histamine, serotonin antagonists or dexamethasone. Furthermore, the core temperature will decrease 10-15°C within 30-60 min. and can be blocked by cyprobeptadine and naloxone. This model provides a system to study the role of eudot~e,~o~ ir,e~iat(,ts in neuroimmunomudulation.