MOLECULAR AND CELLULAR MECHANISMS FOR PERIODONTAL-DISEASES - ROLE OF TH1 AND TH2 TYPE CYTOKINES IN INDUCTION OF MUCOSAL INFLAMMATION

An accumulation of elevated numbers of macrophages (M Phi) and Ig prod ucing cells is associated with localized and chronically inflamed ging iva of patients with adult periodontitis. When gingival lymphocytes we re isolated from inflamed tissues and examined by flow cytometry, appr oximately 20-30% of lymphocytes were CD4(+) T cells. For the analysis of Th1 and Th2 cytokine expression by these CD4(+) T cells, RNA was ex tracted and reverse transcriptase polymerase chain reaction (RT-PCR) w as performed by using specific 5' and 3' primers for IFN-gamma and IL- 2 (Th1), IL-4, IL-5, IL-6, IL-10 and IL-13 (Th2) and p-actin (housekee ping gene). Two distinct cytokine profiles were noted based on the exp ression of selected Th1 and Th2 cytokines. Thus, one pattern was repre sented by the expression of mRNA for IFN-gamma, IL-6, IL-10 and IL-13, while the other case consisted of mRNA for IFN-gamma, IL-6 and IL-13. Except for a few cases, messages for IL-2, IL-4 and IL-5 were not det ected by cytokine-specific RT-PCR. The predominant expression of Th2 c ytokines (e.g. IL-6, IL-10 and IL-13) may contribute to the induction of high B cell responses in local disease sites. On the other hand, la ck of IL-4 may be responsible for the accumulation of M Phi in disease d periodontium. We also investigated whether a relationship exists bet ween IL-4 receptor (IL-4R) expression and M Phi persistence in the abs ence of exogenous IL-4. Gingival M Phi, when compared with monocytes ( MN)/M Phi from peripheral blood mononuclear cells (PBMC), expressed hi gh levels of IL-4R mRNA. When gingival M Phi were incubated with recom binant IL-4 (rIL-4), the cell viability was dramatically reduced by ap optosis. These findings clearly show that the lack of IL-4 may contrib ute to the persistant occurrence of M Phi at the disease site and addi tion of exogenous rIL-4 to gingival M Phi cultures leads to cell death by apoptosis.