COMPLEMENTARY ORGAN EXPRESSION OF IL-1 VS IL-6 AND CSF-1 ACTIVITIES IN NORMAL AND LPS-INJECTED MICE

The specific expression of pro-inflammatory cytokines may affect the f unctioning of organs in different ways. The results of specific cytoki ne bioassays used in this study show a distinct pattern of tissue expr ession of IL-1 IL-6 and CSF-1. Cytokine activity was assessed in condi tioned media (CM) and lysates (LYS), obtained from different organs of control or lipopolysaccharide (LPS)-injected mice; LPS representing a potent inflammatory stimulus. Low constitutive levels of IL-1 could b e demonstrated only in CM/LYS from organs with lymphoreticular functio n, such as the liver, spleen, intestine and lungs. On the other hand, IL-6 and CSF-1 were mainly detected in the CM (and not in lysates) of organs, such as the heart, kidneys, muscle and brain. LPS injection ba sically resulted in an accentuated form of the constitutive pattern. C SF-1 displays a similar pattern of expression to that of IL-6, best de tected in CM after LPS stimulation. Thus, a mirror-image relationship emerges between the patterns of IL-1 and IL-6/CSF-1 expression in two groups of organs: those with lymphoreticular function, which manifest high IL-1 and low IL-6/CSF-1 activity, as compared to organs character ized by highly specialized and potentially vulnerable functions (such as the heart, brain, muscle and kidney), which exhibit high IL-6/CSF-1 and low IL-1 activity. Due to their defensive functions, lymphoreticu lar organs, which are in charge of the 'gates of entry' to the body, m ount extensive IL-1-mediated inflammatory responses, even at the cost of possible tissue-damage, On the other hand, the more vulnerable inte rnal organs mount IL-6/CSF-1-mediated responses which are milder and b ear less potential for tissue damage. The distinct patterns of express ion of pro-inflammatory cytokines in different organs, at steady state or under inflammatory conditions, may shed light on tissue characteri stic homeostatic and defence mechanisms. (C) 1996 Academic Press Limit ed