The ultraviolet radiation (UVR) is known to be a potent modulator of many host immune functions and the exposure of experimental animals to the inflammatory effects of UVR induces depressions in their ability to initiate and effectuate various types of cellular immune responses. In this study, the effects of UV-B (280 320 nm) radiation on resistance to a facultative intracellular bacterium, Listeria monocytogenes (LM), were examined at the cellular level. The numbers of cultivable LM recovered from the spleens of UV-B-irradiated mice were decreased at 2 days postinfection compared with those of untreated control mice. However, the acquired immunity, developed 7 days after immunization with streptomycin (SM)-sensitive LM, in either UV-irradiated, LPS- or IL-1-pretreated mice was less stronger than that developed in untreated, control mice. To elucidate the possible mechanisms underlying the observation that UVR did increase innate immunity but decreased acquired immunity of mice to the infection with LM, the effects of UVR of mice on the production of IFN-r by activated splenocytes and TNF-a by peritoneal macrophages were assessed. Activated splenocytes from UV-irradiated mice exhibited a reduced capacity to produce IFN-r and cultured peritoneal macrophages produced more TNF-a in the presence of LPS during 24 hours after UV radiation. Though TNF-r activity was not detected in the sera of LM-infected mice, intravenous LPS injection induced TNF-r production and UVR decreased TNF activity in sera obtained from LM-infected mice with LPS induction 9 days after irradiation. Although Ia-negative macrophages were predominant in the peritoneal macrophages from untreated control mice, the infection of mice with LM caused a marked increase in Ia expression on peritoneal macrophages. However, UVR resulted in decreased expression of Ia molecule on the peritoneal macrophages during the LM infection. These findings suggest that the dual effects of UVR on the innate and acquired immunity of mice to the LM infection may be associated with altered capacities of splenocytes and peritoneal macrophages of the mice to produce cytokines, in addition to decrease of la molecule expression on the macrophages.
Adaptive Immunity ; Animals ; Cytokines ; Depression ; Immunity, Cellular ; Immunity, Innate ; Immunization ; Listeria monocytogenes* ; Listeria* ; Macrophages ; Macrophages, Peritoneal ; Mice* ; Spleen ; Streptomycin ; Tumor Necrosis Factor-alpha*

It is well known that tumor necrosis factor (TNF-a), interleukin-1, platelet-activating factor (PAF) and arachidonic acid metabolites, such as thromboxane and leukotriens, are major mediators involved in the pathogenesis of endotoxic shock. In this study, we have investigated the effect of pentoxifylline (inhibitor of TNF-a release), BN50739 (PAF antagonist), indomethacin (cyclooxygenase inhibitor) and diethylcarbamazine (lipoxygenase inhibitor) on LPS- induced lethality as well as the relationship between major mediators in endotoxic shock. All inhibitors described above except diethylcarbamazine significantly protected mice against LPS- induced lethality. BN50739 and indomethacin were also effective in protection of TNF-a-induced lethality. The elevation of circulating TNF-a by LPS was significantly blocked by BN50739, but not affected by indomethacin. Convulsion appeared shortly after LPS injection was prevented by BN50739 but not by indomethacin, whereas diarrhea and limited movement was prevented by indomethacin but not by BN50739. These results indicate that i) TNF-a, PAF and cyclooxygenase products are important mediators involved in the pathogenesis of septic shock and ii) TNF-a directly influenced the release or production of PAF as well as cyclooxygenase products, and strongly suggest that i) TNF-a and PAF stimulate the release of each other via positive feedback network but TNF-a and cyclooxygenase products do not form the network and ii) PAF and cyclooxygenase product appear not to affect the release of each other.
Animals ; Arachidonic Acid ; Diarrhea ; Diethylcarbamazine ; Gene Expression* ; Indomethacin ; Interleukin-1 ; Mice ; Pentoxifylline ; Prostaglandin-Endoperoxide Synthases ; Seizures ; Shock, Septic ; Tumor Necrosis Factor-alpha*