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Melatonin plays a pleiotropic role in the immune system of mammals and birds. Endogenous and exogenous melatonin modulates lymphocyte proliferation via specific MT(1), MT(2) and Mel(1c) membrane receptors, although the mechanisms behind this process are poorly understood. The diurnal changes in the expression and function of melatonin membrane receptors within the immune system have so far received little attention. We investigated the day/night differences in melatonin membrane receptor mRNA expression in chicken lymphoid organs and cultured splenocytes and examined the in vitro effect of melatonin and 2-iodomelatonin on the intracellular Ca(2+) concentration ([Ca(2+)](i)) in chicken splenocytes. In whole organs, expression of all subtypes of Mel membrane receptors was observed, and the level did not change significantly with the time of day. Interestingly, we observed a significant increase in the expression of the transcripts of all receptor subtypes in cultured splenocytes isolated at night compared with cells obtained during the day. In chicken spleen leukocytes isolated during the day, melatonin and 2-iodomelatonin increased [Ca(2+)](i), with only 2-iodomelatonin being effective in the 'night' cells. Luzindole modulated the [Ca(2+)](i) increase caused by melatonin receptor agonists: it potentiated the stimulatory effect of melatonin during the day, but counteracted that evoked by 2-iodomelatonin at night. The results of this study demonstrate that melatonin can induce changes in [Ca(2+)](i) in chicken spleen leukocytes that should modulate proliferation. The effect of melatonin on [Ca(2+)](i) is less pronounced at night, possibly caused by receptor desensitization.

Hyporesponsiveness induced by Heligmosomoides polygyrus was quantified and the relationship between TGF-beta and inflammation was identified in BALB/c mice. The immune response and pathological changes modified by neutralization of TGF-beta were characterized in vivo. Nine and twelve days following infection, BALB/c mice were injected intraperitoneally with anti-TGF-beta (1,2,3) antibodies, isotype control antibodies or isosmotic solution. We assessed both Th1 and Th2 related cytokines production ex vivo and in vitro, IgA, the number of CD4+ cells, and eosinophils in the lamina propria and the villus : crypt ratio in the small intestine 6 weeks after infection. The pattern of cytokine production differed in the intestine, peritoneal fluid and serum. In mice infected with H. polygyrus the concentrations of IL-5, IL-12, TNF-alpha and IL-10 were raised in the intestine, but in serum the level of cytokines was diminished below the value observed in uninfected mice. The neutralization of TGF-beta converted the pattern of immune response induced by H. polygyrus. The elevation of cytokines in serum coincided with the reduction of cytokine concentration in the intestine or peritoneum. Neutralization of TGF-beta restored infiltration of eosinophils into the lamina propria of the intestine despite the low level of IL-5. We conclude that H. polygyrus infection suppresses the immune response through pathways involving TGF-beta production or activity and that the Th2 related immune response was not affected by neutralization.