T. Urushibata et al., POLLINOSIS - ETIOLOGIC RELATIONSHIP BETWEEN EXCESSIVE IL-4 PRODUCTIONAND DOWN-REGULATION OF THE INFLAMMATION-SUPPRESSIVE SYSTEM, Acta oto-laryngologica, 1996, pp. 68-73
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.