Effect of methylxanthine derivatives on T cell activation.
In a Phase I-II trial examining the effect of prophylactic administration of pentoxifylline (PTX) on bone marrow transplant-associated morbidity, there was an apparent reduction in the incidence and severity of acute graft-versus-host disease. To determine if PTX might be directly immunosuppressive, its effects on T cell activation and proliferation were examined. PTX and several cogeners were found to directly suppress T cell proliferation in response to phytohemagglutinin, to allogeneic cells in a mixed leukocyte reaction, and to cross-linking the CD3 complex. The effects were dose-related and associated with suppression of secretion of tumor necrosis factor-alpha (TNF alpha). However, the inhibition of proliferation was not solely due to this effect since adding excess recombinant TNF alpha did not restore the proliferative response. These data suggest that PTX may be clinically useful in suppressing allogeneic reactions in bone marrow transplantation.
Marrow Transplant Program, Medical Service, Veterans Affairs Medical Center, Seattle, WA.
J W
JW
Singer
J A
JA
Bianco
G
G
Takahashi
C
C
Simrell
J
J
Petersen
D F
DF
Andrews
D000945:Antigens, Differentiation, T-Lymphocyte; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D018801:CD2 Antigens; D017252:CD3 Complex; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline