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 control of the lens alpha-A crystallin promoter. Expression of human IL-1 beta was restricted to the eye; neither the protein nor its mRNA were detected in various other organs of the Tg mice. The Tg mice develop severe ocular inflammation shortly after birth, which affects the lens and other eye tissues and apparently allows the release of IL-1 into the circulation. Here we report that the Tg mice exhibit decreased responsiveness to IL-1 and lipopolysaccharide (LPS), as compared to their wild-type littermate controls: (1) when injected with IL-1 the Tg mice produced lower levels of serum amyloid A than their controls; (2) thymocytes of the Tg mice responded less vigorously in culture to stimulation with IL-1; and (3) Tg mice showed lower morbidity and mortality than their controls when injected with toxic amounts of LPS. These data 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.