Production of interleukin 10 and transforming growth factor beta in concomitant allergy and autoimmunity.

BACKGROUND: The immunologic relationship between T(H)1-type autoimmune disorders and T(H)2-type allergic disorders and the role of T-cell regulation in humans is as yet unclear. The regulatory cytokine production capacity of individuals with concomitant allergy and T(H)1-type autoimmunity may provide insight into the role of T-cell regulation in both disorders. OBJECTIVES: To examine the production capacity of interleukin 10 (IL-10) and transforming growth factor beta (TGF-beta), 2 regulatory cytokines, in individuals with concomitant allergic rhinitis and T(H)1-type autoimmune diagnoses and to compare that capacity with that in individuals with allergic rhinitis only and individuals with neither diagnosis. METHODS: Seventeen case subjects and 17 age-, sex-, and ethnicity-matched controls with allergic rhinitis only were recruited from an allergy clinic. Fourteen matched controls with neither diagnosis were recruited from the general population. Peripheral blood mononuclear cells were obtained and cultured with and without mitogen stimulation (lipopolysaccharide and phytohemagglutinin). Cytokine levels from culture supernatants were measured by enzyme-linked immunosorbent assay. RESULTS: Cases with allergic rhinitis and autoimmune diseases had significantly lower unstimulated day 3 IL-10 levels compared with controls with allergic rhinitis only (P = .05) and significantly lower stimulated day 5 TGF-beta levels compared with controls with neither diagnosis (P = .02). Cases had consistently lower regulatory capacity compared with both control groups, as measured by an additive index using IL-10 and TGF-beta levels. CONCLUSION: Individuals with concomitant allergic rhinitis and T(H)1-type autoimmune disorders have a lower regulatory cytokine production capacity than individuals with allergic rhinitis only and those with neither diagnosis.

Regulation of proteoglycan synthesis by leukotriene d4 and epidermal growth factor in bronchial smooth muscle cells.

Extracellular matrix (ECM) expansion contributes to airway remodeling in asthma. This study examines the effect of leukotriene D4 (LTD4), combined with epidermal growth factor (EGF), on proteoglycan synthesis by cultured human bronchial smooth muscle cells (BSMCs). LTD4 plus EGF stimulated proliferation of BSMCs with increased versican synthesis. Further, versican mRNA splice variants, V0 and V1, were differently regulated in BSMCs by LTD4 plus EGF. Synthesis of [35S]-methionine labeled versican V0, as a percentage of total versican, was doubled. This upregulation was confirmed by Western analysis. Synthetic changes were paralleled by alterations in versican V0 mRNA. The effects of LTD4 and EGF on proteoglycan synthesis were inhibited by montelukast. Similar upregulation of versican V0 was observed in arterial smooth muscle cells (ASMCs) stimulated with LTD4 plus EGF as measured by western and reverse transcriptase-polymerase chain reaction analyses. Changes in ECM in the asthmatic airway may parallel those in atherosclerotic lesions where proliferating ASMCs synthesize a versican-rich expanded ECM. Inhibition of these processes could lead to reduced tissue expansion in the early phases of asthma progression.