INTERLEUKIN-1-ALPHA EXPRESSION IS INDUCIBLE BY CHOLINERGIC STIMULATION IN THE RAT ADRENAL-GLAND

Interleukin-1-like immunoreactivity has earlier been demonstrated by immunohistochemistry in the noradrenaline-containing chromaffin cells of the rat adrenal gland [Schultzberg et al. (1989) Neuroscience 30, 805-810; Schultzberg et al. (1987) J. Neurosci. Res. 18, 184 189]. In this study, we examine the regulation, upon cholinergic stimulation, of the expression of the cytokine interleukin-1-alpha in the rat adrenal gland. Interleukin-1-alpha and interleukin-1-alpha mRNA levels in the adrenal gland are affected by systemic administration of the cholinergic agonists nicotine (0.5 mg/kg. i.p.) and carbachol (0.5 mg/kg, i.p.). Both drugs cause an increase in interleukin-1-alpha mRNA levels. In contrast to the increased mRNA levels, nicotine and carbachol reduce the interleukin-1-alpha protein level measured in the rat adrenal gland: nicotine by approximately 30%, 60 min after injection, and carbachol by approximately 55%, 30 min after injection. The interleukin-1-alpha protein level returns to control level 90 min after nicotine injection, and 120 min after carbachol injection. We thus found a large. constitutively expressed and inducible pool of interleukin-1-alpha in the rat adrenal gland, which appears to be sensitive to cholinergic stimulation and which may be responsible for some of the local and systemic effects of interleukin-1-alpha. Experiments with Escherichia coli lipopolysaccharide show that this substance, which induces interleukin-1 expression and secretion in macrophages, is also able to induce the expression of interleukin-1-alpha mRNA and interleukin-1-alpha in the adrenal gland when injected at the dose of 2 mg/kg, i.p.