REDUCED SUSCEPTIBILITY TO IL-1 AND ENDOTOXIN IN TRANSGENIC MICE EXPRESSING IL-1 IN THEIR LENS

To learn about the effects of chronic exposure to IL-1 we generated a transgenic (Tg) mouse line that expresses human IL-1 beta under the co ntrol of the lens alpha A crystallin promoter. Expression of human IL- 1 beta was restricted to the eye; neither the protein nor its mRNA wer e detected in various other organs of the Tg mice, The Tg mice develop severe ocular inflammation shortly after birth, which affects the len s and other eye tissues and apparently allows the release of IL-1 into the circulation. Here we report that the Tg mice exhibit decreased re sponsiveness to IL-1 and lipopolysaccharide (LPS), as compared to thei r wildtype littermate controls: (1) when injected with IL-1 the Tg mic e produced lower levels of serum amyloid A than their controls; (2) th ymocytes of the Tg mice responded less vigorously in culture to stimul ation with IL-1; and (3) Tg mice showed lower morbidity and mortality than their controls when injected with toxic amounts of LPS, These dat a suggest that chronic exposure to IL-1 in the Tg mice induces partial resistance to this cytokine, analogous to the reduced responsiveness to IL-1 in animals pretreated with this proinflammatory cytokine. (C) 1996 Academic Press Limited