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Infect. Immun., May 1995, 1688-1697, Vol 63, No. 5
D Sturm, J Menzel, B Gottstein and P Kern
An involvement of cellular immunity in alveolar echinococcosis is strongly
suggested by the intense granulomatous infiltrations observed around the
hepatic parasite lesions. However, the basis of cellular immunoregulation
in patient with alveolar echinococcosis is poorly understood. The present
report shows a comparative analysis of lymphoid cell function in peripheral
blood mononuclear cells (PBMC) of 16 patients with alveolar echinococcosis
and of healthy individuals. Our in vitro restimulation studies with crude
Echinococcus multilocularis antigen demonstrated that PBMC from patients
with alveolar echinococcosis were responsive to challenge with parasitic
antigen as measured by lymphoid cell proliferation. In this system, we also
evaluated cytokine expression at the gene and protein levels after
stimulation with E. multilocularis antigen. Analysis of cytokine mRNA
expression revealed distinct patterns of cytokine expression in patients
and normal donors. By using reverse transcriptase PCR, we could demonstrate
that the TH1 cytokine transcripts interleukin-2 (IL- 2) and gamma
interferon (IFN-gamma) are present in PBMC from patients with alveolar
echinococcosis. Moreover, it was found that stimulation with E.
multilocularis antigen induced or enhanced the expression of the TH2
cytokine IL-3, IL-4, IL-10, and especially IL-5 mRNAs in PBMC from 13 of 16
patients with alveolar echinococcosis. Two patients who were examined after
radical surgery, as well as another patient with a stable course of the
disease under continuous chemotherapy, were not able to generate the same
pattern of cytokine response and had no evidence of IL-5 mRNA synthesis. In
contrast to the frequent expression of TH2 cytokine mRNAs observed in
patients with alveolar echinococcosis, PBMC cultures from normal donors
showed prominent IL-2 and IFN-gamma mRNA expression but weak IL-3, IL-4,
and IL-10 mRNA expression. Most interestingly, IL-5 mRNA was substantially
absent in PBMC from healthy individuals. In accordance with the mRNA
studies, it was found that E. multilocularis antigen induced the secretion
of large amounts of IL-5 and intermediate amounts of IFN-gamma in patients
with alveolar echinococcosis, whereas large amounts of IFN-gamma and no or
threshold amounts of IL-5 were detected in supernatants from healthy
individuals. Collectively, the present study provides the first evidence
that a TH2 immune response is gradually activated during the course of E.
multilocularis infection, indicating a critical role for IL-5 in the
manifestation of human alveolar echinococcosis.
Copyright © 1995, American Society for Microbiology
Interleukin-5 is the predominant cytokine produced by peripheral blood mononuclear cells in alveolar echinococcosis
Section of Infectious Diseases and Clinical Immunology, University of Ulm, Germany.
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