Immunomodulating therapy with rIL-2 and interferon alpha-induces in vivo expression of Bcl-2, Fas (APO-1/CD95), and Fas ligand on peripheral lymphocytes (a pilot study).
The first Phase I Trial with a combination of IL-2 and IFN-alpha was published in 1989. There are still some questions though, concerning the in vivo effects of this combination on lymphocytes. We designed a prospective pilot study to evaluate in vivo effects of low dose IL-2 and IFN-alpha combination on expression of Bcl-2, FAS (Apo-1/CD 95), Fas Ligand, IL-2 receptor (CD25), and HLA-DR on peripheral lymphocytes in patients with advanced renal cell carcinoma. After initiation of the immunomodulating therapy, Bcl-2 expressing lymphocytes increased significantly on day 3 (p < 0.025), Fas (Apo-1/CD95) expressing lymphocyte increased significantly on day 5 (p < 0.003), Fas ligand expressing lymphocytes increased significantly on day 3 (p < 0.004), HLA-DR expressing lymphocytes increased significantly on day 5 (p < 0.003), and IL-2 receptor (CD25) expressing cells increased significantly on day 5 (p < 0.01). We conclude that immunomodulating therapy induces in vivo expression of Bcl-2, Fas (Apo-1) and Fas Ligand in lymphocytes significantly.
Demir
G
G
University of Istanbul, Cerrahpasa School of Medicine, Medical Oncology Department, Turkey. gdemir@turknet
Ozguroglu
M
M
Sayhan
N
N
Molinas-Mandel
N
N
Demirelli
F
F
Buyukunal
E
E
Tuzuner
N
N
Serdengecti
S
S
Berkarda
B
B
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D053222:Fas Ligand Protein; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013997:Time Factors; D019014:fas Receptor / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006684:HLA-DR Antigens; D016898:Interferon-alpha; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D019014:fas Receptor