Effects of recombinant tumor necrosis factor (rHuTNF alpha) on human neutrophils and monocytes: in vitro, ex vivo and in vivo.
In in vitro experiments, tumor necrosis factor (rHuTNF alpha) was found to inhibit spontaneous and directed migration of normal human neutrophils and monocytes. RHuTNF alpha showed no chemoattractant activity. In conjunction with a Phase-2 clinical trial, we also studied in vivo rHuTNF alpha effects on neutrophil and monocyte number and function. At the time of maximal plasma TNF levels (30 min), marked neutropenia and monocytopenia were observed. Isolated neutrophils were activated for superoxide production but were unable to migrate. Monocyte migration was inhibited at later times. Neutrophil migratory function recovered between 4 and 8 h but was again depressed at 24 h. The data demonstrate the complexity of the response to TNF, comprising direct and indirect effects which are concentration-, time- and place-dependent. They further suggest that the only neutrophils and monocytes available for participation in an anti-tumor activity of TNF in vivo are those present in the tumor at the outset.
Schell-Frederick
E
E
Medizinische Universitäts Klinik I, Köln, West Germany.
Tepass
T
T
Lorscheidt
G
G
Pfreundschuh
M
M
Schaadt
M
M
Diehl
V
V
D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007958:Leukocyte Count / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects*; D011994:Recombinant Proteins; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides