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Correlation of Th1-Type Cytokine Expression and Induced Proliferation to Lipopolysaccharide

¹ Institute of Allergy and Immunology, ² Department of Pediatrics, and ³ Department of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin, Israel

Correspondence and requests for reprints should be addressed to Michael R. Goldberg, M.D., Ph.D., Institute of Allergy and Immunology, Assaf Harofeh Medical Center, Zerifin, 70300, Israel. E-mail: goldbergsm{at}yahoo.com

Recent evidence from mouse models indicates that neonatal exposure to lipopolysaccharide (LPS) can prevent experimentally induced allergic disease. Furthermore, we noted that human cord blood mononuclear cells (CBMC) have an increased proliferative response to LPS relative to their respective maternal peripheral blood mononuclear cells (PBMC). We sought, therefore, to examine the cytokine expression profile induced by LPS in CBMC and its relationship to the LPS-mediated proliferative response. CBMC and maternal PBMC were evaluated for IL-10, IL-4, IL-13, IL-12, and IFN- expression after LPS stimulation by real-time PCR. IFN- secretion was detected by enzyme-linked immunosorbent assay. LPS increased IFN- and IL-13, but decreased IL-4 expression in CBMC (P < 0.024, P < 0.014, and P < 0.027, respectively). In PBMC, however, no significant changes in expression were noted after LPS stimulation. Stimulation by LPS significantly increased the secretion of IFN- in CBMC compared with PBMC at the two concentrations analyzed (1 ng/ml, P < 0.048; 10,000 ng/ml, P < 0.003). The magnitude of the LPS-mediated proliferative effect in CBMC directly correlated to the level of induction of IFN- (P < 0.01), but inversely correlated to the induced levels of IL-4 and IL-13 (P < 0.01 and P = 0.01, respectively). No association of the CBMC proliferative response to IL-12 or IL-10 was noted. Thus, a high proliferative response to LPS in CBMC correlates with a change from a Th2- to Th1-induced cytokine expression profile. Since early exposure to LPS may protect against allergic disease, one may speculate that an aberrant response to LPS may increase the likelihood of developing overt disease in susceptible individuals.

Key Words: asthma hygiene hypothesis • chemokines • innate immunity

CLINICAL RELEVANCE These results describe for the first time a mechanism by which human cord blood mononuclear cells may be influenced by the innate immune system to mitigate against Th2-mediated disease.