Pentoxifylline and meclofenamic acid treatment reduces clinical manifestations in a murine model of AIDS.
C57/BL/6 mice infected with LP-BM5 MuLV virus developed an AIDS-like disease (MAIDS) with splenomegaly, leukopenia, thrombocytopenia, anemia, decreased numbers of helper/inducer and suppressor/cytotoxic T-cells and decreased production of interferon alpha. We have shown previously that HIV-associated Kaposi's sarcoma tissue contains high levels of prostaglandin E2 (PgE2), and this inhibits interferon synthesis through a cAMP-dependent second-messenger process. In this study we treated groups of MAIDS-infected mice with combinations of pentoxifylline, an agent which increases cAMP and inhibits phosphodiesterases, and sodium meclofenamic acid, a PgE2 inhibitor. Treated mice showed: 1) significantly higher total leukocyte and platelet counts, 2) higher total L3T4+ (helper/inducer) and Lyt-2+ (suppressor-cytotoxic) T-cell population. Pathologic examination also showed significantly less hepatosplenomegaly and lymphadenopathy in animals treated with pentoxifylline and meclofenamic acid. Partly, PgE2-induced suppression of interferon alpha production may mediate expression of retrovirus infection in this murine model of AIDS.
Stadler
I
I
Department of Internal Medicine, Buffalo General Hospital, State University of New York.
Chadha
K C
KC
Nakeeb
S
S
Toumbis
C
C
Butsch
J
J
Mathur
N
N
Munschauer
F
F
Vladutiu
A
A
Satchidanand
S K
SK
Ambrus
J L
JL
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008297:Male; D008469:Meclofenamic Acid / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D010431:Pentoxifylline / Q000627:therapeutic use*
D008469:Meclofenamic Acid; D010431:Pentoxifylline