Pleiotropic effects of cytokines: clinical and preclinical studies.
Cytokines have diverse and pleiotropic effects including immunologic, hematopoietic and pro-inflammatory activities. A total of 135 patients have been treated in a series of phase I clinical trials utilizing five different recombinant cytokines: granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), interleukin 3 (rhIL-3) interleukin 4 (rhuIL-4), and interleukin 6 (rhIL-6). The toxicity, maximum tolerated dose and biologic activities were determined. Hematopoietic, immunologic and pro-inflammatory effects were noted during therapy with these agents. Prominent effects on lymphocyte and monocyte functional activities were demonstrated. The diversity of biologic effects in vivo demonstrates the pleiotropic nature of the cytokines investigated and the difficulties encountered in their in vivo evaluation.
Bukowski
R M
RM
Experimental Therapeutic Program, Cleveland Clinic Cancer Center, Ohio.
Olencki
T
T
McLain
D
D
Finke
J H
JH
D001772:Blood Cell Count; D017321:Clinical Trials, Phase I as Topic; D016207:Cytokines / Q000009:adverse effects / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D007377:Interleukin-3 / Q000009:adverse effects / Q000627:therapeutic use; D015847:Interleukin-4 / Q000009:adverse effects / Q000627:therapeutic use; D015850:Interleukin-6 / Q000009:adverse effects / Q000627:therapeutic use; D016173:Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use; D009369:Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D016207:Cytokines; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor