Evidence for an abnormal profile of interleukin-4 (IL-4), IL-5, and ?-interferon (?-IFN) in peripheral blood T cells from patients with allergic eosinophilic gastroenteritis

Abstract

Allergic eosinophilic gastroenteritis is characterized by elevated total IgE, specific IgE to food antigens, and eosinophilia of tissue and blood. Because the lymphokines IL-4, IL-5, and γ-interferon, regulate IgE synthesis, and eosinophilopoiesisin vitro, we examined whether there is an imbalance in their production in allergic eosinophilic gastroenteritis. To explore this hypothesis, three adult patients with allergic eosinophilic gastroenteritis were studied. Flow cytometric studies of peripheral blood mononuclear cells from these patients did not reveal evidence of T cell activation or disturbance of T cell numbers or subsets. T cells were capable of normal mitogenic activationin vitro. IL-4 and IL-5 production were markedly elevated with mitogenic stimulation. Most IL-4 and IL-5 production was by CD4⁺ T cells. Synthesis of IL-5 by CD4⁺ T lymphocytes in three patients and CD8⁺ T lymphocytes in two patients occurred in the absence of mitogen. Mitogen-stimulated GM-CSF and γ-interferon synthesis by CD4⁺ T cells was normal. Lymphokine mRNA in total cellular RNA derived from endoscopic biopsies was examined by reverse transcription/polymerase chain reaction. Mucosal biopsies from control subjects and most biopsies from allergic eosinophilic gastroenteritis patients contained less than 10⁻⁸ μg IL-5 mRNA/1 μg total cellular mRNA. γ-Interferon mRNA was not detected by reverse transcription/ polymerase chain reaction in biopsies from patients with allergic eosinophilic gastroenteritis but was present in controls. These lymphokine abnormalities are consistent with the elevated IgE and eosinophilia seen in allergic eosinophilic gastroenteritis and suggest that strategies targeting T lymphocytes may be efficacious in treatment of this disease.