Correlation of @entity19 susceptibility to @entity5 , parasite and bacterial challenge with altered cell-mediated immunity following systemic exposure to the @entity5 promoter XXXX .

@entity5 @entity19 @entity4515 @entity4514 @entity4996 @entity320
@entity4514 ( @entity4515 ), the most potent of the @entity5 promoting @entity4996 , modulates function in several immunoresponsive cells following in vitro exposure. Since suppression of cellular mechanisms capable of limiting @entity5 and infections can adversely affect health, these experiments were designed to evaluate relevant components of cell-mediated immunity (CMI) following in vivo @entity4515 exposure, and to determine the biological significance of any alterations utilizing assays of host resistance. Adult, female B6C3F1 @entity19 were administered 0.2, 2.0, 20.0 or 40.0 micrograms @entity4515 /g body weight subcutaneously over a two-week period. Mechanisms of cell-mediated host resistance were assessed by quantitating natural killer (NK), cytotoxic T-lymphocyte (CTL) and macrophage-mediated lysis of radiolabelled @entity5 target cells, and macrophage-induced cytostasis in @entity5 cell populations. Macrophages from @entity4515 -treated @entity19 were cytostatic to @entity5 cells, inhibiting up to 90% of growth in cultured @entity5 cells, but were not tumoricidal. Furthermore, pyran-elicited (primed) macrophages, which are activated to fully cytotoxic states by in vitro exposure to lipopolysaccharide, were inhibited in tumoricidal activation by in vivo @entity4515 exposure. The induction of responsive but not cytotoxic macrophages by in vivo @entity4515 exposure is consistent with the enhanced resistance to Listeria bacterial challenge, and increased susceptibility to B16F10 @entity5 and Trichinella parasitic challenges observed in these @entity19 . Furthermore, previous reports of decreased in vitro NK activity following in vivo @entity4515 exposure and present observations of correlative decreases of in vivo NK activity (55% decrease in @entity19 exposed to 20 micrograms @entity4515 /g) suggest an important role for NK activity in limiting in vivo B16F10 @entity320 growth. CTL effector function was less susceptible to @entity4515 -induced suppression than NK function at similar dosages, further supporting a predominant role of macrophages and NK cells or possibly other effector functions in the resistance to Listeria, Trichinella, or B16F10 challenge. Nevertheless, significant suppressive effects of @entity4515 on CTL function at higher dosages cannot be excluded as contributing to altered host resistance to these agents. These studies demonstrate that in vivo exposure to @entity4515 can modify cell-mediated mechanisms of host resistance with coincident alterations in the incidence of @entity5 .
