IL-4 AND IL-5 MESSENGER-RNA AND PROTEIN IN BRONCHIAL BIOPSIES FROM PATIENTS WITH ATOPIC AND NONATOPIC ASTHMA - EVIDENCE AGAINST INTRINSIC ASTHMA BEING A DISTINCT IMMUNOPATHOLOGIC ENTITY

Intrinsic (nonatopic) asthma is considered to be a distinct pathogenet ic variant of asthma since, unlike extrinsic (atopic) asthma, patients with the disease are skin test-negative to common aeroallergens, and have total serum IgE concentrations within the normal range. Neverthel ess, the recent demonstration of increased numbers of cells expressing the high-affinity IgE receptor in bronchial biopsies from atopic and nonatopic asthmatic subjects, together with epidemiologic evidence ind icating that serum IgE concentrations relate closely to asthma prevale nce regardless of atopic status, suggests that IgE-mediated mechanisms may participate in the pathogenesis of both atopic and nonatopic asth ma. Furthermore both variants of the disease are associated with bronc hial mucosal eosinophilic inflammation. Interleukin-4 (IL-4) is an ess ential cofactor for IgE synthesis, and there is strong evidence that I L-5 plays a major role in eosinophil accumulation in asthmatic inflamm ation. For these reasons we compared the expression of IL-4 and IL-5 m RNA and protein product using a semiquantitative reverse transcriptase -polymerase chain reaction (RT-PCR) amplification, in situ hybridizati on, and immunohistochemistry in bronchial biopsies from symptomatic at opic and nonatopic asthmatic subjects and atopic and nonatopic control s. The results showed that as compared with controls, biopsies from bo th groups of asthmatic subjects had increased numbers of IL-4 and IL-5 mRNA copies relative to beta-actin mRNA as detected by RT-PCR. Simila rly, in situ hybridization and immunohistochemistry demonstrated incre ased numbers of cells expressing IL-4 and IL-5 mRNA and protein in ast hmatic subjects, irrespective of their atopic status. We conclude that individuals with either atopic or nonatopic asthma show infiltration of the bronchial mucosa with cells expressing Th2-type cytokines, prov iding further evidence for similarities in the immunopathogenesis of t hese clinically distinct forms of asthma.