Effect of Efalizumab on neutrophil and monocyte functions in patients with psoriasis.
We evaluated the effect of efalizumab on neutrophil and monocyte functions. The in vitro pre-incubation with efalizumab concentrations similar to those reached during in vivo therapy almost completely saturated CD11a binding sites without affecting the membrane expression of CD11b, CD128a or CD128b. There was a significant reduction in the chemotactic activity of the pre-treated cells toward three different chemo-attractants, whereas their phagocytic capacity and production of oxygen radicals remained unchanged. One month after the administration of efalizumab to five patients with psoriasis (T1) circulating neutrophil counts increased by 34% from pre-therapy (T0) with no change in the number of monocytes. In the same patients the CD11a binding sites on phagocytes were >90% saturated, and there was also a significant down-modulation on neutrophils (44% of T0) and monocytes (63% of T0). In line with in vitro results, efalizumab treatment caused a significant deficiency in the chemotactic properties of neutrophils and monocytes, but no changes in phagocytosis, oxidative burst, production of pro-inflammatory cytokines or the membrane expression of CD11b, CD128a and CD128b. Our findings suggest that neutrophils and monocytes may be among the targets of efalizumab activity in patients with psoriasis.
Rheumatology Unit Istituto Ortopedico Galeazzi IRCCS, University of Milan, Milan, Italy. franco.capsoni@unimi.it
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D000166:Acridines / Q000494:pharmacology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens / Q000096:biosynthesis; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000166:Acridines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens; D017382:Reactive Oxygen Species; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C033472:10,10'-dimethyl-9,9'-biacridinium; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate; C472181:efalizumab