POLLINOSIS - ETIOLOGIC RELATIONSHIP BETWEEN EXCESSIVE IL-4 PRODUCTIONAND DOWN-REGULATION OF THE INFLAMMATION-SUPPRESSIVE SYSTEM

Previous findings suggest a bi-directional relationship between the im mune and endocrine systems, which may expand to a major inflammation-r egulatory mechanism, although its mechanism is largely unknown, especi ally in the human body. Lymphokine and neuroendocrine peptide hormones have been identified as two major groups of immunologic mediators. Th e particularly pivotal molecules among them are interleukin 1 (IL-1), considered to be a mediator of inflammation, and ACTH, whose activatio n is induced by IL-1. Among the important functions of lymphokines rel ated to atopic inflammation is the regulation of IgE secretion from B cell through the action of IL-4, produced from the Th2 subset stimulat ed by IL-1, as a switch factor. IL-4 is the major IgE secretagogue. IL -4 is, moreover, a potent suppressive stimulant of IL-1 secretion. In this study, we tested the hypothesis whether a immunologic interaction exists in patients with allergic rhinitis to Japanese cedar pollen. W e performed immunohistochemical staining of IL-1 beta, interleukin 1 r eceptor (IL-1r) and interleukin-4 (IL-4) in the nasal tissue, and eval uated serum levels of the biochemical mediators involved in the inflam mation-regulatory mechanism: IL-1 beta, IL-4, interleukin 1 receptor a ntagonist (IL-1ra), IgE, cortisol, and ACTH before, during, and after allergen-provoked rhinitis in pollinosis sufferers. Our morphological study showed that, even before the pollen season, large amounts of IL- 4 and IL-1r, exclusive of IL-1 beta, were produced in the nasal tissue of patients with seasonal pollinosis. IL-1-positive cells were observ ed in small amounts in the same tissue, but the quantity was probably enough to cause secretion of intrinsic IL-4 to produce sufficient IgE for atopic inflammation. Upon immunoenzymatic measurement of serum IL- 4, even before the pollen season, almost all atopic patients also show ed a higher IL-4 level than controls. Serum IgE data also showed a hig h level before the pollen season in atopic patients. This evidence sug gests that atopic patients have already set the first step of inflamma tory event not only in the nasal epithelium but also generally even be fore inhaling proper quantity and quality of the allergen. On the othe r hand, although atopic patients had inflammation, they did not show a n extremely high value of serum IL-1, regarded as inflammatory lymphok ine, compared with non-atopic individuals. In contrast, a higher serum level of IL-1ra was observed before and during the pollen season in a topic patients, subsiding to normal level after the season. Serum leve ls of both cortisol and ACTH did not show a high value in atopic patie nts during the season. These results demonstrate that excessive IL-4 p roduction of atopic patient causes down-regulated transformation of IL -1 and up-regulated secretion of IL-1ra generally, followed by failure to increase secretion of ACTH from hypophysis and cortisol generally, resulting in defective performance of a specifically useful function of the anti-inflammatory mechanism.