Interferon Gamma

(BAN, rINN)
Synonyms: IFNgamma; Interferoni gamma; Interferonigamma; Interferonum Gamma.
Cyrillic synonym: Интерферон Гамма.

💊 Chemical information

CAS — 98059-18-8 (interferon gamma-1a); 98059-61-1 (interferon gamma-1b).
ATC — L03AB03.
ATC Vet — QL03AB03.

Pharmacopoeias.

Eur. includes Interferon Gamma1b Concentrated Solution.

Ph. Eur. 6.2

(Interferon Gamma-1b Concentrated Solution; Interferoni Gamma-1b Solutio Concentrata). It is a solution of the N-terminal methionyl form of interferon gamma. It is produced by a method based on recombinant DNA technology using bacteria as host cells. It is a clear, colourless or slightly yellowish liquid. The pH of the solution is 4.5 to 5.5. Store in airtight containers at a temperature of −70°. Protect from light.

Nomenclature.

Interferon gamma may be derived from immunologically stimulated T-lymphocytes (hence its former name of immune interferon) or produced by recombinant DNA technology. Similarly to interferon alfa, protein variants of interferon gamma are designated by a number and further qualified by a letter to indicate the amino-acid sequences at terminal positions 1 and 139:
interferon gamma-1a has at position 1 hydrogen, cysteine, tyrosine, and cysteine and at position 139 arginine, alanine, serine, glutamine, and a hydroxyl group
interferon gamma-1b, formerly known as interferon gamma2a, has at position 1 hydrogen and methionine and at position 139 a hydroxyl group Interferon gamma derived through recombinant DNA technology is labelled (rbe).

💊 Adverse Effects

As for interferons in general

💊 Precautions

As for interferons in general. Interferon gamma in high doses has been
shown to increase the incidence of abortions in primates and should be avoided during pregnancy.

💊 Interactions

As for interferons in general.

💊 Antiviral Action

As for interferons in general.

💊 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 to 8 hours after subcutaneous injection. Half-lives of 38 minutes (intravenous dosage), 2.9 hours (intramuscular dosage), and 4.9 to 5.9 hours (subcutaneous dosage) have been reported.

💊 Uses and Administration

Interferon gamma is a cytokine with 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 and reduce the frequency of serious infections in patients with severe malignant osteopetrosis. Interferon gamma-1b is given in a dose of 50 micrograms/m 2 body-surface (1 million units/m 2 ) three times weekly by subcutaneous injection. Patients with a body-surface less than 0.5 m 2 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 (see below). Interferon gamma-n1 has also been used for the treatment of cutaneous T-cell lymphomas.
1. Marciano BE, et al. Long-term interferon-γ therapy for patients with chronic granulomatous disease. Clin Infect Dis 2004; 39: 692–9.

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 disease1 but was of no benefit in a study in burn-related infections.2 For the conventional management of these infections, see Whipple’s Disease and Skin Infections.
1. Schneider T, et al. Treatment of refractory Whipple disease with interferon-γ. Ann Intern Med 1998; 129: 875–7
2. Wasserman D, et al. Interferon-γ in the prevention of severe burn-related infections: a European phase III multicenter trial. Crit Care Med 1998; 26: 434–9.
MYCOBACTERIAL INFECTIONS. Experience with interferons for nontuberculous 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 given interferon gamma alone.1,2 Beneficial responses have also been reported after use of interferon alfa3 or gamma4 as an adjunct to antimycobacterial therapy in HIV-negative patients with mycobacterial infections unresponsive to conventional therapy. Interferon alfa has been tried as an adjunct to conventional therapy in multibacillary leprosy.5 Inhaled interferon alfa6 or gamma7 may be a useful adjunct to conventional antimycobacterial treatment for pulmonary tuberculosis. For discussion of these infections and their standard treatment, see Leprosy, Nontuberculous Mycobacterial Infections, and Tuberculosis.
1. Squires KE, et al. Interferon-γ and Mycobacterium avium-intracellulare infection. J Infect Dis 1989; 159: 599–600
2. Squires KE, et al. Interferon-γ treatment for Mycobacterium avium-intracellulare complex bacillemia in patients with AIDS. J Infect Dis 1992; 166: 686–7
3. Maziarz RT, et al. Reversal of infection with Mycobacterium avium intracellulare by treatment with alpha-interferon in a patient with hairy cell leukemia. Ann Intern Med 1988; 109: 292–4
4. Holland SM, et al. Treatment of refractory disseminated nontuberculous mycobacterial infection with interferon gamma: a preliminary report. N Engl J Med 1994; 330: 1348–55
5. Ganapati R, et al. A multicenter study of recombinant interferonalpha2b in the treatment of multibacillary leprosy. Int J Lepr 1997; 65: 495–7
6. Giosuè S, et al. Effects of aerosolized interferon-α in patients with pulmonary tuberculosis. Am J Respir Crit Care Med 1998; 158: 1156–62
7. Condos R, et al. Treatment of multidrug-resistant pulmonary tuberculosis with interferon-γ via aerosol. Lancet 1997; 349: 1513–15.

Cryptogenic fibrosing alveolitis.

In a preliminary study1 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.2 A later study3 involving 330 patients with CFA found that interferon gamma 1-b did not affect progressionfree survival or pulmonary function; however, a trend toward lower mortality was seen in patients who received interferon gamma-1b compared with those given placebo. A subsequent study4 to characterise the molecular effects of subcutaneous interferon gamma-1b versus placebo reported that interferon gamma-1b affected CFA through multiple pathways and could be of potential benefit. A randomised, prospective study5 comparing interferon gamma-1b and colchicine (given for 24 months) in patients with mild-to-moderate CFA reported that 15.6% of patients treated with interferon gamma-1b and 38.8% of those given colchicine died. Patients treated with interferon gamma-1b also showed a higher forced vital capacity after 24 months of treatment. A review6 of the use of interferon gamma-1b in the management of CFA found that efficacy of interferon gamma-1b was inconsistent with regard to changes in pulmonary function and mortality, although studies suggested that interferon gamma1b may be of benefit in earlier-stage disease. A meta-analysis7 of randomised controlled studies evaluating the use of interferon gamma-1b in the treatment of CFA concluded that interferon gamma-1b therapy was associated with reduced mortality.
1. Ziesche R, et al. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. N Engl J Med 1999; 341: 1264–9
2. King TE. Interferon gamma-1b for the treatment of idiopathic pulmonary fibrosis. N Engl J Med 2000; 342: 974–5
3. Raghu G, et al. A placebo-controlled trial of interferon gamma1b in patients with idiopathic pulmonary fibrosis. N Engl J Med 2004; 350: 125–33
4. Strieter RM, et al. Effects of interferon-γ 1b on biomarker expression in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2004; 170: 133–40
5. Antoniou KM, et al. Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis. Eur Respir J 2006; 28: 496–504
6. Pacanowski MA, Amsden GW. Interferon gamma-1b in the treatment of idiopathic pulmonary fibrosis. Ann Pharmacother 2005; 39: 1678–86
7. Bajwa EK, et al. Interferon-γ1b therapy in idiopathic pulmonary fibrosis: a metaanalysis. Chest 2005; 128: 203–6.

Leishmaniasis.

Interferon gamma has been tried both systemically and locally as an adjunct to standard treatment of leishmaniasis with encouraging results. A review1 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.2 For cutaneous infections, intralesional interferon gamma has been shown to be effective3 but less so than intralesional antimony compounds.4 Subcutaneous interferon gamma (with antimony given intravenously) was no more effective than antimony alone when given as a short course over 10 days.5 However, encouraging responses have been reported in patients who have failed to respond to antimony compounds alone.6
1. Murray HW. Interferon-gamma and host antimicrobial defense: current and future clinical applications. Am J Med 1994; 97: 459–67
2. Sundar S, et al. Response to interferon-
γ plus pentavalent anti
mony in Indian visceral leishmaniasis. J Infect Dis 1997; 176: 1117–19
3. Harms G, et al. Effects of intradermal gamma-interferon in cutaneous leishmaniasis. Lancet 1989; i: 1287–92
4. Harms G, et al. A randomized trial comparing a pentavalent antimonial drug and recombinant interferon-γ in the local treatment of cutaneous leishmaniasis. Trans R Soc Trop Med Hyg 1991; 85: 214–16
5. Arana BA, et al. Efficacy of a short course (10 days) of highdose meglumine antimonate with or without interferon-γ in treating cutaneous leishmaniasis in Guatemala. Clin Infect Dis 1994; 18: 381–4
6. Falcoff E, et al. Clinical healing of antimony-resistant cutaneous or mucocutaneous leishmaniasis following the combined administration of interferon-γ and pentavalent antimonial compounds. Trans R Soc Trop Med Hyg 1994; 88: 95–7.

Osteopetrosis.

Interferon gamma has been tried in the treatment of malignant osteopetrosis. A study1 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.
1. Key LL, et al. Long-term treatment of osteopetrosis with recombinant human interferon gamma. N Engl J Med 1995; 332: 1594–9.

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.1 In two studies2,3 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 study2 but remained high in the other.3 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.4 Interferon alfa has been tried in subacute cutaneous lupus erythematosus5,6 and discoid lupus erythematosus.6 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 reports7,8 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 scleroderma9 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.10 Interferons have also been used for the treatment of warts.
1. Souillet G, et al. Alpha-interferon treatment of patient with hyper IgE syndrome. Lancet 1989; i: 1384
2. Reinhold U, et al. Recombinant interferon-γ in severe atopic dermatitis. Lancet 1990; 335: 1282
3. Boguniewicz M, et al. Recombinant gamma interferon in treatment of patients with atopic dermatitis and elevated IgE levels. Am J Med 1990; 88: 365–70
4. MacKie RM. Interferon-α for atopic dermatitis. Lancet 1990; 335: 1282–3
5. Nicolas J-F, Thivolet J. Interferon alfa therapy in severe unresponsive subacute cutaneous lupus erythematosus. N Engl J Med 1989; 321: 1550–1
6. Thivolet J, et al. Recombinant interferon α2a is effective in the treatment of discoid and subacute cutaneous lupus erythematosus. Br J Dermatol 1990; 122: 405–9
7. Kolde G, et al. Treatment of urticaria pigmentosa using interferon alpha. Br J Dermatol 1995; 133: 91–4
8. Lippert U, Henz BM. Long-term effect of interferon alpha treatment in mastocytosis. Br J Dermatol 1996; 134: 1164–5
9. Polisson RP, et al. A multicenter trial of recombinant human interferon gamma in patients with systemic sclerosis: effects on cutaneous fibrosis and interleukin 2 receptor levels. J Rheumatol 1996; 23: 654–8
10. Fushimi M, et al. Eosinophilic pustular folliculitis effectively treated with recombinant interferon-γ: suppression of mRNA expression of interleukin 5 in peripheral blood mononuclear cells. Br J Dermatol 1996; 134: 766–72.

💊 Preparations

Proprietary Preparations

Arg.: Imufor†; Imukin; Austral.: Imukin; Austria: Imukin; Belg.: Immukine; Cz.: Imukin; Denm.: Imukin; Fin.: Imukin; Fr.: Imukin; Ger.: Imukin; Gr.: Imukin; Hong Kong: Immukin; Irl.: Immukin; Ital.: Gammakine†; Imukin; Jpn: Biogamma; Ogamma†; Neth.: Immukine; Norw.: Imukin; NZ: Imukin; Port.: Imukin; Spain: Imukin; Swed.: Imukin; Switz.: Imukin; UK: Immukin; USA: Actimmune.
Published December 01, 2018.