83. Variation in cytokine expression levels in different immune compartments, and organ-specific effects of stress

Abstract

Pro/anti-inflammatory cytokines are key players in the etiology of several diseases and in immune activation, and stress hormones were reported to modulate their levels. Our recent studies identified unique leukocyte populations that kill autologous tumor cells which are considered “immune-resistant”. These include marginating leukocytes residing in the lungs and liver capillaries, and specifically activated NK cells (e.g., pit cells). However, the differential effects of stress on leukocytes of each compartment are poorly understood. Here we examined potential variations in cytokine profiles in different organs of F344 rats, and the effects of a 10 h wet-cage stress exposure. Following stress, blood was withdrawn by cardiac puncture, and spleens, lungs, and livers were harvested, weighed, and frozen. Tissues were homogenized in 2 ml PBS, and pro- and anti-inflammatory cytokine levels were quantified using ELISA. In the plasma, only IL-12 was detectable, and its levels were reduced by stress. In the spleen, stress reduced IL-12, VEGF, and IL-1-beta levels. Conversely, in the liver stress increased the levels of IL-1-beta, IFN-gamma, VEGF, and IL-6. No stress effects were evident in the lungs. TNF-alpha, MMP-9, TGF-beta, and IL-10 are currently being quantified. These organ-specific effects of stress may be attributed to tissue-specific responses towards stress hormones, or to redistribution of specific leukocyte subpopulations. These non-exclusive hypotheses, and the alleged stress-induced shift in the pro/anti-inflammatory cytokine balance, are currently being studied.