This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chikkala, N. F. Articles by Finke, J. H. Search for Related Content PubMed PubMed Citation Articles by Chikkala, N. F. Articles by Finke, J. H.

Interactive Effects of -Interferon A/D and Interleukin 2 on Murine Lymphokine-activated Killer Activity: Analysis at the Effector and Precursor Level¹

Department of Immunology and Cancer, Research Institute [N. F. C., I. L., J. U., J. S., J. H. F.], and Department of Pathology, Laboratory Medicine [R. T.], Cleveland Clinic Foundation, Cleveland, Ohio 44195

Studies from our laboratory and others have demonstrated that -interferon (IFN) can regulate natural killer cells and lymphokine-activated killer (LAK) cell activation. In vitro experiments have shown that IFN has differential effects on both natural killer cells and LAK activity when combined with interleukin 2 (IL2); IFN synergized with IL2 to augment natural killer cells activity while it suppressed the IL2-induced LAK response. Here we demonstrated that IFNA/D can also regulate IL2-induced LAK activity in vivo with enhanced or suppressed activity depending on the IFNA/D dose. The enhanced response was observed with the combination when 80,000 units/day of IFNA/D were used and was detectable in the spleen, lung, and peritoneum. When a high dose of IFNA/D was combined with IL2, a moderate reduction in LAK activity was noted in the spleen and peritoneum. In contrast, a high dose IFNA/D augmented IL2-induced LAK activity in the lung even though it reduced the level of cellular infiltration. We have also evaluated the effect that IL2, IFNA/D, and IL2 plus IFNA/D have on the frequency of LAK precursors in the spleen and lung using limiting dilution analysis. Treatment of normal mice with IL2 alone increased the frequency of LAK precursor (LAKp) in the lung. This increase was associated with an infiltration of Thy-1⁺, asialo-GM1⁺, Lyt-2^- lymphocytes into the lungs. Moreover, treatment with IL2 plus IFNA/D enhanced the frequency of LAKp over that observed with IL2 alone. Treatment with the combination did not change the phenotype of LAKp in the lung from that seen with IL2. The increase in LAKp frequency induced by the combined treatment may not be a direct effect of IFNA/D on precursor cells since IFNA/D alone did not increase the frequency of LAKp in vivo or in vitro when added to limiting dilution analysis cultures. In contrast to what occurred in the lung, a consistent increase in LAKp was not seen in the spleen after treatment with IL2 or with the combination, although LAK activity was observed. These results demonstrated that in addition to inducing lytic activity from LAK effectors in vivo, IL2 treatment increased the number of precursor cells within the lung. Moreover, IFNA/D in combination with IL2 influenced the level of LAKp in situ.

¹ This study was supported by a grant from the American Cancer Society (IM 469).

² A portion of the data presented here was obtained as part of Ph.D. dissertation.

³ To whom requests for reprints should be addressed at Research Institute, Department of Immunology and Cancer, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.

Received 11/14/88. Revised 11/13/89. Accepted 11/15/89.

This article has been cited by other articles:

				T R L Griffiths and J K Mellon Evolving immunotherapeutic strategies in bladder and renal cancer Postgrad. Med. J., June 1, 2004; 80(944): 320 - 327. [Abstract] [Full Text] [PDF]

				E. M. Messing, J. Manola, G. Wilding, K. Propert, J. Fleischmann, E. D. Crawford, J. E. Pontes, R. Hahn, and D. Trump Phase III Study of Interferon Alfa-NL as Adjuvant Treatment for Resectable Renal Cell Carcinoma: An Eastern Cooperative Oncology Group/Intergroup Trial J. Clin. Oncol., April 1, 2003; 21(7): 1214 - 1222. [Abstract] [Full Text] [PDF]

				J. I. Clark, E. R. Gaynor, B. Martone, S. C. Budds, R. Manjunath, R. C. Flanigan, W. B. Waters, and J. A. Sosman Daily Subcutaneous Ultra-Low-Dose Interleukin 2 with Daily Low-Dose Interferon-{{alpha}} in Patients with Advanced Renal Cell Carcinoma Clin. Cancer Res., September 1, 1999; 5(9): 2374 - 2380. [Abstract] [Full Text] [PDF]