Chin-Hung Lin

Abstract

In this study, the suppressive effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on peritoneal macrophage killing of H238 target cells and the potential for reversal of the immunosuppressive effect by IL-4 and interferon-γ (IFN-γ) were investigated. The responsiveness of naive and peptone-activated macrophages was compared. The cytolytic activity for tumor cells of these effector cells was measured by percent lysis of 3H-thymidine labeled Herpes simplex virus type 2-transformed tumor cells (H238). After 18-24 hours of incubation with TGF-β or IL-10, the cytolytic activity of macro-medium alone. The immunosuppressive effect of TGF-β or IL-10 on non-activated macrophages was dose-dependent, with as little as 1 ng/ml TGF-β or 25.0 ng/ml IL-10, suppressing the cytolytic activity. After coincubation with TGF-β (5ng/ml) and IL-4 (200ng/ml) or IFN-γ (400 unit/ml), inhibition in the killing activity of macrophages was reversed by 20-30% when compared to controls incubated with TGF-β alone. IL-4 and IFN-γ both partially reversed the immunosuppressive effects of TGF-β on macrophages. When 10% proteose peptone was injected into mice to activate macrophages, the findings show that TGF-β could suppress non-activated macrophage cytotoxicity, but did not inhibit the cytotoxicity of peptone-activated cells. The killing activity of resting macrophages was significantly inhibited by 50 ng/ml of IL-10. When H238 tumor-bearing mice were treated with anti-TGF-β antibody (Ab), the results show that the production of tumor necrosis factor-α (TNF-α), a cytokine known to directly destroy tumors, in H238 tumor-bearing mice without treatment is lower than in H238 tumor-bearing mice with anti-TGF-β Ab treatment.

LLU Discipline

Microbiology

Department

Microbiology

School

Graduate School

First Advisor

James D. Kettering

Second Advisor

Daila S. Gridley

Third Advisor

Thomas A. Linkhart

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

1993

Date (Title Page)

6-1993

Language

English

Library of Congress/MESH Subject Headings

Transforming Growth Factor beta; Interleukin-10; Macrophages; Cytokines; Immunosuppression

Type

Thesis

Page Count

vii; 53

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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