Chronic granulomatous disease treatment

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Interferon-/ 143 amino acids, glycosylated E. coli Chronic granulomatous disease Approved for sale In clinical trials for treatment of cancer and viral diseases... 

Ahlin, A. et al., Gamma interferon treatment of patients with chronic granulomatous disease is associated with augmented production of nitric oxide by polymorphonuclear neutrophils, Clin. Diagn. Lab Immunol, 6, 420, 1999. 

In mature neutrophils, interferon-7induces the expression of FC7RI, increases antibody-dependent cytotoxicity, primes the ability to generate reactive oxidants and selectively stimulates protein biosynthesis. These effects are described in detail in Chapter 7. Additionally, this cytokine has been used clinically for the treatment of chronic granulomatous disease (CGD), which is associated with an increased susceptibility to infections due to an impairment of NADPH oxidase function ( 8.2). 

Chin, T. W.,Stiehm, E. R.,Falloon, J., and Gallin, J. I., Corticosteroidsin treatment of obstructive lesions of chronic granulomatous disease. J. Pediatr. Ill, 349-352 (1987). 

Interferon 3-la (Avonex) and interferon 3-lb (Betaseron) are used in the treatment of multiple sclerosis. Interferon y-lb (Actimmune) is used to prevent and diminish the severity of infections associated with chronic granulomatous disease and for delaying the progression of severe, malignant osteopetrosis. 

H. Other considerations Interferon gamma-lb has been designated an orphan product for use in the treatment of chronic granulomatous disease, renal cell carcinoma, and severe congenital osteoporosis. 

Lysis of antibody-coated red cells through the products of the respiratory burst appears to be linked to phagocytosis Neutrophils from patients with chronic granulomatous disease lysed antibody-coated erythrocytes less effectively than PMNs from norma subjects in suspension, but when phagocytosis was prevented by attachment of the erythrocytes to plastic or by treatment with colchicine, PMNs from the patients with chronic granulomatous disease lysed the red cells normally. 

Actimmunc (Interferon gamma-lb) approved for treatment of chronic granulomatous disease. 

Williamson PR, Kwon-Chung KJ, Gallin JI Successful treatment of Paecilomyces variotii infection in a patient with chronic granulomatous disease and review of Paecilomyces species infections. Clin Infect Dis 1992 14 1023-1026. 

CaiUot D, Bassaris H, McGeer A, Arthur C, Prentice HG, Seifert W, De Beule K. Intravenous itraconazole followed by oral itraconazole in the treatment of invasive pulmonary aspergillosis in patients with hematologic mahgnancies, chronic granulomatous disease, or AIDS. Qin Infect Dis 2001 33(8) e83-90. 

In patients who absolutely require further treatment, successful desensitization can be achieved (147). Two patients with chronic granulomatous disease who had previously been intolerant of co-trimoxazole completed a 5-day desensitization protocol with a good clinical outcome (148). 

Interferon ylb 143 amino acids— glycosylated Actimmune (Genentech) E. coli Treatment of chronic granulomatous disease... 

In a study of haematopoietic stem cell transplant for chronic granulomatous disease patients who were transplanted with either matched related donor (n=4) or matched unrelated donor (n=7), four patients experienced grade I skin acute graft-versus-host disease that responded to topical treatment and all were alive (between 1 and 8 years) after transplant [169 ]. 

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