Recombinant human interleukin 3 induces proliferation of inflammatory cells and keratinocytes in vivo.
In this preclinical study we investigated the effect(s) of recombinant human (rh) interleukin 3 (IL-3) on hemopoietic differentiation and attempted to evaluate possible clinical side effects of this hemopoietic growth factor. Rh IL-3, derived from either Escherichia coli or Chinese hamster ovary, was administered subcutaneously to 16 rhesus monkeys (by pairs) at different doses (11, 33, and 100 micrograms/kg/day) for 14 days. During the 2nd week of administration white blood cell counts increased 2- to 3-fold mainly because of a dose-dependent elevation of basophils (up to 40% of white blood cells) and eosinophils. In addition, moderate to marked elevations of plasma histamine levels were measured. Transient diarrhea and an erythematous skin rash with generalized cutaneous lesions that was not restricted to the injection sites were present in 3 of 6 animals treated with E. coli-derived rh IL-3 (1 of 2 animals that received 33 micrograms/kg and 2 of 2 that received 100 micrograms/kg) and 2 of 6 monkeys treated with Chinese hamster ovary-derived rh IL-3 (1 of 2 that received 33 micrograms/kg and 1 of 2 that received 100 micrograms/kg), respectively. Histopathologic and immunohistologic evaluation of skin specimens revealed a perivascular mononuclear cell infiltrate interspersed with numerous mast cells. Signs of vasculitis were absent. The density of the perivascular infiltrate correlated not only with the dose of IL-3 but also with the duration of the skin eruption. Moreover, hyperproliferation of basal keratinocytes resulting in acanthosis was observed in lesions persisting for 1 and 4 days as also evidenced by a significant (p less than 0.01) increase in Ki-67 (a proliferation-associated marker)-positive basal keratinocytes.
Volc-Platzer
B
B
Department of Dermatology I, University of Vienna, Austria.
Valent
P
P
Radaszkiewicz
T
T
Mayer
P
P
Bettelheim
P
P
Wolff
K
K
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects; D004890:Erythema / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006632:Histamine / Q000097:blood; D006801:Humans; D007249:Inflammation; D007377:Interleukin-3 / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity*; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects; D017730:Ki-1 Antigen; D008253:Macaca mulatta; D008297:Male; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000473:pathology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D007377:Interleukin-3; D017730:Ki-1 Antigen; D011994:Recombinant Proteins; D006632:Histamine