Cytokine therapy

The role of cytokine therapy in the management of radiation accident victims has been summarized (152). In GoiBnia in Brazil in 1987, eight radiation accident victims were treated with GM-CSF one month after radiation exposure. Marked increases in granulocyte production were induced in five persons, although this did not prevent death. 

Metastatic renal cell carcinoma has a poor prognosis and resists conventional chemotherapy. Immunotherapy with IL-2 and/or IFN-a is currently regarded as the most effective therapy with, however, modest response rates of 15-20%. Similar results are also observed in patients with metastatic melanoma and the response to IFN-a and IL-2 correlates with the occurrence of tumor-infiltrating CD4+ T-lymphocytes identified in aspirates from melanoma metastases. Determination of these cells therefore seems to be a method to predict responders prior to the initiation of cytokine therapy. 

Wigginton, J. and Wiltrout, R. 2002IL-12/IL-2 combination cytokine therapy for solid tumors translation from benchside to bedside. Expert Opinion on Biological Therapy 2(5), 513-524. 

Several pro-inflammatory cytokines, such as TNFa, IL-1, IL-6, are important in the initiation and maintenance of various autoimmune diseases, such as RA, CD, and psoriasis. Thus, targeted therapies, which have been developed to inhibit their activity, have resulted in clinical improvement of these patients. Currently, there are three TNFa inhibitors (etanercept, infliximab, and adalimumab) and one IL-1 receptor antagonist (anakinra) that have been approved for the treatment of at least one of these diseases. In addition, a number of other anti-cytokine therapies are in clinical development. The TNFa antagonists will be reviewed here. 

Galvani, D. W., Cawley, J. C. (1992). Cytokine Therapy. Cambridge University Press, U.K. 

Other neutrophil disorders are related to specific defects in key neutrophil enzymes or processes these are described in detail in the following sections. Many of these diseases are rare and have only recently been discovered. The survival of such patients is possible today only because these specific defects are now more readily identified, and because infections can be carefully managed using a wide range of potent antibiotics. In some patients (e.g. those with CGD), cytokine therapy may again prove useful. 

Hutson TE, Quinn DI. Cytokine therapy a standard of care for metastatic renal cell carcinoma Clin Geni-tourin Cancer. 2005 4 181-186. 

Jaffe, S. Kramer, S. Sherwin, and R.G. Crystal. 1991. Organ specific cytokine therapy. Local activation of mononuclear phagocytes by delivery of an aerosol of recombinant interferon-gamma to the human lung. /. Clin. Invest. 88 ... 

Ioannou, Y., and Isenberg, D. A., Current evidence for the induction of autoimmune rheumatic manifestations by cytokine therapy. Arthritis Rheum. 43, 1431-1442 (2000). 

Yang W, Wang Q, Kanes SJ, Murray JM, Nishikura K. Altered RNA editing of serotonin 5-HT2C receptor induced by interferon implications for depression associated with cytokine therapy. Brain Res Mol Brain Res 2004 124 70-78. 

Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R (2002) Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry 7 468-473. 

Two remarkable successes of cytokine therapy are the treatment of multiple sclerosis with interferon-p and the treatment of rheumatoid arthritis and inflammatory bowel disease with tumor necrosis factor-a inhibitors. 

O Hearn DJ, Leiferman KM, Askin F, Georas SN. Pulmonary infiltrates after cytokine therapy for stem cell transplantation. Massive deposition of eosinophil major basic protein detected by immunohistochemistry. Am J Respir Grit Care Med 1999 160(4) 1361-5. 

Asnis LA, Gaspari AA. Cutaneons reactions to recombinant cytokine therapy. J Am Acad Dermatol I995 33(3) 393 I0. 

Experimental data support the hypothesis that IFNy is antifibrogenic this may be a consequence of cytokine therapy. Some of the most important classical cellular actions of IFNy are summarized in Table 22-6. 

Oleksowicz L, Puszldn E, Mrowiec Z, et al. Alterations in platelet function in patients receiving interleukin-6 as cytokine therapy. Cancer Invest 1996 14 307-16. 

Alveolar da = 2-5 da = 0.02-0.05 Sedimentation and diffusion Diffusion Slow inspiratory flowrate High tidal volume Breath holding 2-6 sec Vaccines, cancer cytokine therapy (asthma, inflammation)... 

Maini RN, Taylor PC. Anti-cytokine therapy for rheumatoid arthritis. Ann... 

Start cytokine therapy if mustine dose is thought to be high enough to cause bone marrow suppression or if there is a fall in blood count ... 

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