Stabilized analogs of thymopentin. 3. Evaluation of ketomethylene pseudopeptides for antiarthritic properties.
This study analyzed the role of ketomethylene pseudopeptides of thymopentin as potential agents for the treatment of arthritis. The analogs were tested in vivo using assessment of inflammation and antibody production in the mouse type II collagen arthritis model and the rat adjuvant arthritis model. The compounds were also tested for immune-potentiating activity in vitro using induction of the lymphocyte marker, Thy-1.2, in mouse spleen cells and stimulation of T-cell proliferation. The results show that certain of the compounds exhibit disease-remitting properties for arthritis as evidenced by reduction of paw swelling in the mouse and rat models and decreased incidence of disease in the mouse model. The active compounds were dose specific and represented a range in efficacy. In spite of effects on arthritis, type II collagen antibody levels were not altered in the mouse model. Selected compounds also exhibited immune potentiating properties as evidenced by induction of Thy-1.2 expression and stimulation of T-cell proliferation. The absence of effect of the compounds on type II collagen antibody production suggests that the antiarthritic activity of the effective compounds results from alteration of cell-mediated immunity.
Smith
R L
RL
Orthopaedic Research Laboratory, Stanford University Medical Center, California 94305-5341, USA.
Dousman
L
L
Waud
W R
WR
DeGraw
J I
JI
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D016305:Thymopentin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016305:Thymopentin