Immunomodulation by the new synthetic thiazole derivative tiprotimod. 3rd communication: influence on host resistance to microorganisms, tumors and on experimental immune disorders.
To evaluate the influence of [2-(3-carboxy-1-probylthio)-4-methyl-1,3-thiazole]acetic acid (tiprotimod, HBW 538) on the host defense mechanisms, a number of experimental studies in different animal models were performed. The prophylactic treatment of NMRI mice with tiprotimod significantly prolonged the mean survival time of the animals after intravenous infection with Candida albicans 200/175 and increased the resistance to the fungal infection to 180% in comparison to controls. In vitro the drug showed no direct fungistatic or fungicidal activity. In an experimental model of persistent systemic candidiasis Balb/c mice infected intravenously with Candida albicans were treated with the immunomodulator tiprotimod after the fungal colonization of kidney was manifested (3 days post infection). The treatment of the mice after the infection resulted in a reduction of the infectious load and the abscess formation in kidney as well as in a decrease of numbers of yeasts in the urine. In the syngeneic B16 melanoma tumor model tiprotimod significantly prolonged the medium survival time and reduced the number of visuable metastases in the lungs even when applied after resection of the primary tumor graft. Tiprotimod also beneficially influenced the course of the disease in two murine graft-vs-host models (hemolytic anemia and immune complex glomerulonephritis) which lead to a B cell mediated autoimmune disease with fatal outcome. The application of the drug in the induction phase mitigated the development of the diseases and prevented animals from dying.(ABSTRACT TRUNCATED AT 250 WORDS)
Schorlemmer
H U
HU
Research Laboratories of Behringwerke AG, Marburg/Lahn, Fed. Rep. of Germany.
Dickneite
G
G
Hänel
H
H
Dürckheimer
W
W
Sedlacek
H H
HH
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology / Q000382:microbiology; D000818:Animals; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology; D005260:Female; D006087:Graft vs Host Reaction / Q000187:drug effects; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D051381:Rats; D018805:Sepsis / Q000276:immunology / Q000382:microbiology; D016038:Skin Transplantation; D013844:Thiazoles / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D013844:Thiazoles; C061180:tiprotimod