CORTICOTROPIN-RELEASING HORMONE IS INVOLVED IN CONDITIONED STIMULUS-INDUCED REDUCTION OF NATURAL-KILLER-CELL ACTIVITY BUT NOT IN CONDITIONED ALTERATIONS IN CYTOKINE PRODUCTION OR PROLIFERATION RESPONSES
L. Perez et Dt. Lysle, CORTICOTROPIN-RELEASING HORMONE IS INVOLVED IN CONDITIONED STIMULUS-INDUCED REDUCTION OF NATURAL-KILLER-CELL ACTIVITY BUT NOT IN CONDITIONED ALTERATIONS IN CYTOKINE PRODUCTION OR PROLIFERATION RESPONSES, Journal of neuroimmunology, 63(1), 1995, pp. 1-8
Research from our laboratory has demonstrated that the presentation of
an aversive conditioned stimulus produces pronounced suppression of s
everal in vitro measures of immune status. The present study was desig
ned to evaluate the role of central corticotropin-releasing hormone (C
RH) in the mechanisms mediating these conditioned effects. The aversiv
e conditioned stimulus was a distinct environment that had previously
been associated with electric footshock. Lewis rats received intravent
ricular administration of either buffered saline or a dose of the CRH-
selective receptor antagonist alpha-helical CRH((9-41)) (0, 0.5, 5, or
50 mu g) prior to exposure to the aversive conditioned stimulus or ho
me cage control treatment. The aversive conditioned stimulus produced
decreases in splenic natural killer cell activity, splenocyte responsi
veness to the mitogens concanavalin A (ConA), phytohemagglutinin (PHA)
, lipopolysaccharide (LPS), and the combination of ionomycin and phorb
ol myristate acetate (PMA), blood leukocyte responsiveness to ConA and
PHA, and the production of interleukin-2 and interferon-gamma by acti
vated splenocytes. The conditioned stimulus also produced an increase
in plasma levels of corticosterone. Pretreatment with alpha-helical CR
H((9-41)) completely blocked the conditioned stimulus-induced suppress
ion of natural killer cell. activity. The CRH antagonist had no attenu
ative effect on the conditioned suppression of splenocyte or blood leu
kocyte proliferation in response to mitogens, or the production of int
erleukin-2 or interferon-gamma by activated splenocytes. There was als
o no effect of alpha-helical CRH((9-41)) on the conditioned stimulus-i
nduced increase in plasma corticosterone. These findings suggest that
conditioned stimulus-induced suppression of natural killer cell activi
ty is mediated by a mechanism that involves activity at central CRH re
ceptors, and that this conditioned modulation is independent of HPA ac
tivation. Furthermore, these results indicate that the mechanisms invo
lved in conditioned stimulus-induced suppression of proliferative or c
ytokine production responses are distinct from those involved in the m
odulation of natural killer cell activity.