Monograph: |
Interferon Gamma
Adverse Effects
As for interferons in general (see Interferon Alfa)
Precautions
As for interferons in general (see Interferon Alfa).
Interactions
As for interferons in general (see Interferon Alfa).
Antiviral Action
Interferons are produced by virus-infected cells and confer protection on uninfected cells of the same species. They affect many cell functions and have, in addition to their antiviral activity, antiproliferative and immunomodulating properties. Interferon gamma in particular is a potent macrophage-stimulating factor.
Pharmacokinetics
Interferons are not absorbed from the gastrointestinal tract. Peak plasma concentrations of interferon gamma-1b occur about 4 hours after intramuscular injection and about 7 hours after subcutaneous injection. Half-lives of 38 minutes (intravenous administration), 2.9 hours (intramuscular administration), and 5.9 hours (subcutaneous administration) have been reported.
Uses and Administration
Interferon gamma has antiviral and immunomodulating effects. Interferon gamma-1b is used for its action as a macrophage-stimulating factor as an adjunct to antimicrobial therapy in chronic granulomatous disease. It is also used to delay time to disease progression in patients with severe malignant osteopetrosis.
Interferon gamma-1b is given in a dose of 50 micrograms/m2 body-surface (1 million units/m2) three times weekly by subcutaneous injection. Patients with a body-surface less than 0.5 m2 should receive 1.5 micrograms/kg body-weight three times weekly.
Interferon gamma-1b is also under investigation for the treatment of cryptogenic fibrosing alveolitis .
Interferon gamma-n1 has also been used.
Bacterial infections.
In addition to its use to control infections in chronic granulomatous disease, interferon gamma was used with some success as an adjunct to antibacterials in a patient with Whipple's disease but was of no benefit in a study in burn-related infections. For the conventional management of these infections, see Whipple's Disease,and Skin Infections.
Mycobacterial infections.
Interferon alfa has been tried as an adjunct to conventional therapy in multibacillary leprosy. Experience with interferons for opportunistic mycobacterial infections in patients with AIDS is limited. Interferon gamma given with antimycobacterials produced beneficial responses in 3 patients with Mycobacterium avium complex infections, but produced no response or only a transient response in 3 others who received interferon gamma alone.
Beneficial responses have also been reported after use of interferon alfa or gamma as an adjunct to antimycobacterial therapy in HIV-negative patients with mycobacterial infections unresponsive to conventional therapy.
Inhaled interferon alfa or gamma may be a useful adjunct to conventional antimycobacterial treatment for pulmonary tuberculosis.
For discussion of these infections and their standard treatment, see Leprosy, Opportunistic Mycobacterial Infections, and Tuberculosis .
Cryptogenic fibrosing alveolitis.
In a preliminary study in patients with cryptogenic fibrosing alveolitis who had not responded to treatment with corticosteroids or to other immunosuppressive therapy, lung capacity increased in 9 patients given interferon gamma-1b with prednisolone for 12 months, but deteriorated in 9 who were treated with prednisolone alone for the same period. The study was, however, criticised for its methodology and the statistical significance of its findings questioned. A later study involving 330 patients with cryptogenic fibrosing alveolitis did not find interferon gamma 1-b to be of benefit.
Leishmaniasis.
Interferon gamma has been tried both systemically and locally as an adjunct to standard treatment of leishmaniasis with encouraging results. A review of the use of interferon gamma in non-viral infections concluded that interferon gamma was effective when combined with antimony compounds for treatment failures in visceral leishmaniasis and could enhance the response to initial therapy in untreated patients. However, the response to adjunctive interferon gamma was limited in patients with a high degree of resistance to antimony compounds. For cutaneous infections, intralesional interferon gamma has been shown to be effective but less so than intralesional antimony compounds. Subcutaneous administration of interferon gamma with antimony given intravenously was no more effective than antimony alone when given as a short course over 10 days. However, encouraging responses have been reported in patients who have failed to respond to antimony compounds alone.
Osteopetrosis.
Interferon gamma has been tried in the treatment of malignant osteopetrosis . A study in 14 patients found that interferon gamma-1b increased bone resorption. In 11 who received this treatment for 18 months there was stabilisation or improvement in clinical condition and a reduction in the frequency of serious infection.
Skin disorders.
Interferons have been tried in skin disorders in which IgE levels are raised. Subcutaneous interferon gamma improved eczema and reduced serum-IgE concentration in one patient, but the condition gradually returned within a week of stopping treatment. In two studies subcutaneous interferon gamma given to patients with severe atopic dermatitis and raised serum-IgE concentrations resulted in improvement of the skin condition; IgE concentrations were reduced in one study but remained high in the other. Subcutaneous interferon alfa, however, was unsuccessful in 2 patients with very severe atopic dermatitis; serum-IgE concentrations and severity of the skin condition remained unaffected. Interferon alfa has been tried in subacute cutaneous lupus erythematosus and discoid lupus erythematosus. Although marked improvement generally occurred, the condition tended to recur within several weeks of stopping treatment. For discussion of the conventional treatment of eczema and of lupus erythematosus, see Systemic Lupus Erythematosus.
There have been reports of the successful use of interferon alfa to control the symptoms of urticaria associated with mastocytosis.
Interferons have also been proposed for antifibrotic therapy in the management of diffuse scleroderma A multicentre study of interferon gamma in scleroderma found that cutaneous symptoms might be improved but that treatment was associated with an unacceptable incidence of adverse effects. Interferon gamma has also been tried in eosinophilic pustular folliculitis.
Interferons have also been used for the treatment of warts (see under Interferon Alfa).
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