Interferons autoimmunity

Tran A, Beusnel C, Montoya ML, Lussiez V, Hebuterne X, Rampal P. Hepatite autoimmune de typ 1 revelee par un traitement par interferon. [Autoimmune... 

Autoimmune Disease. Figure 2 Generation of autoreactivity. APC, antigen presenting cell IFN, interferon LPS, lipopolysaccharide MHC, major histocompatibility complex T, T-lymphocyte TCR, Tcell (antigen) receptor TLR, toll like receptors. For details see text. 

For the pathogenesis of multiple sklerosis, autoimmune T-lymphocy tes play a predominant role, which are directed against components of the neural myelin sheath. T-lymphocy tes by secreting cytokines such as interferon y maintain the chronic inflammation which destructs the myelin sheath. Also cytotoxic T-lymphocytes may participate directly. The cause of multiple sklerosis is unknown. Significantly increased antibody titers against several vitusses, mostly the measles virus, point to a (latent) virus infection initiating the disease. 

Interferon beta-la (AVONEX , Rebif ), interferon beta-lb (Betaferon ), and interferon beta (Fiblaferon ) are applied in multiple sclerosis to reduce both frequency and severity of disease incidents and for the treatment of severe viral infections. In multiple sclerosis, DFN- 3 proteins modulate the destruction of myelin in the cause of the autoimmune reaction. 

Soos, J. and Johnson, H. 1999. Interferon-T. Prospects for clinical use in autoimmune disorders. BioDrugs 11(2), 125-135. 

Issues regarding the influence of duration or intensity of exposure in relation to effect on autoimmune disease processes are questions that have not been established, with some inconsistencies seen in the epidemiologic studies (Table 25.2). Dose or intensity of silica exposure affects the clearance from the lung and silica-containing macrophages can be translocated to pulmonary lymph nodes. Increased production of immunoglobulins and of lymphocyte-derived interferon-gamma is seen at these sites.49... 

Interferons alpha and beta have major effects on the immune system, such as increasing the expression of MHC-I and MHC-II. Interferon-a is elevated in patients with idiopathic lupus and it is believed to be involved in its pathogenesis [105] therefore, it is not surprising that therapy with these interferons can lead to autoimmunity. 

Wandl, U.B. et al., Lupus-like autoimmune disease induced by interferon therapy for myeloproliferative disorders, Clin. Immunol. Immunopathol., 65, 70, 1992. 

Interferons (IFN) are glycoproteins that, among other products, are released from virus-infected cells. In neighboring cells, interferon stimulates the production of "antiviral proteins." These inhibit the synthesis of viral proteins by (preferential) destruction of viral DNA or by suppressing its translation. Interferons are not directed against a specific virus, but have a broad spectrum of antiviral action that is, however, species-specific. Thus, interferon for use in humans must be obtained from cells of human origin, such as leukocytes (IFN-a), fibroblasts (IFN-P), or lymphocytes (IFN-y). Interferons are also used to treat certain malignancies and autoimmune disorders (e.g., IFN-a for chronic hepatitis C and hairy cell leukemia IFN-p for severe herpes virus infections and multiple sclerosis). 

Ribavirin capsules/oral solution/interferon alfa-2b Patients with autoimmune... 

Capsules/Tablets/Oral solution-There are significant adverse events caused by ribavirin capsules/interferon alfa-2b or peginterferon alfa-2b therapy, and ribavirin tablets/peginterferon alfa-2a therapy, including severe depression and suicidal ideation, hemolytic anemia, suppression of bone marrow function, autoimmune and infectious disorders, pulmonary dysfunction, pancreatitis, and diabetes. 

Alpha interferons, including peginterferon alfa-2a, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. 

Autoimmune disorders Development or exacerbation of autoimmune disorders, including myositis, hepatitis, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus have been reported in patients receiving alpha interferon. 

Alpha interferons, including peginterferon alfa-2b, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Closely monitor patients with periodic clinical and laboratory evaluations. Withdraw from therapy patients with persistently severe or worsening signs or symptoms of... 

Peg Interferon Alfa 2b (PEG-Intron) [Antiviral/ Immunomodulator] WARNING Can cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disord s. Monitor pts closely Uses Rx Hep C Action Immune modulation Dose 1 mcg/kg/wk SQ 1.5 mcg/kg/wk combined w/ ribavirin Caution [C, X if used w/ ribavirin /-] w/ Hx psychiatric Contra Autoimmune H, decompensated Uvct Dz, hemoglobinopathy Disp Vials 50, 80, 120, 150 mcg/0.5 mL Redipen 50, 80,120,150 mcg/5 mL reconstitute w/ 0.7 mL w/ sterile water SE D ession, insomnia, suicidal behavior, GI upset, neutropenia, thrombocytopenia, alopecia, pruritus Interactions t Myelosuppression W/ antineoplastics t effects OF doxorubicin, theophylline t neurotox W7 vinblastine EMS See Peg Interf on Alfa-2a may cause flu-like Sxs... 

Interferons—Family of immune system signal proteins that interfere with the ability of viruses to infect cells. Interferons have been genetically engineered to provide treatments by weakening immune response in autoimmune disease such as multiple sclerosis, or by strengthening immune response in diseases like hepatitis C. 

The most frequent adverse effects are flu-like symptoms increased body temperature, feeling ill, fatigue, headache, muscle pain, convulsion, dizziness, hair thinning and depression. Erythema, pain and hardness on the spot of injection are also frequently observed. Interferon therapy may cause immunosuppression. Also various interferon induced autoimmune syndromes were reported. 

Infrequent reactions to interferon therapy include proteinuria, renal toxicity, autoimmune disease, thyroid disease, ophthalmic toxicity, pulmonary dysfunction (pulmonary infiltrates, pneumonitis, and pneumonia), and cardiovascular effects (tachycardia, arrhythmia, hypotension, cardiomyopathy, and myocardial infarction). Rarely, the body may develop antibodies against interferons that inhibit their effectiveness. 

Interferons are contraindicated in individuals with autoimmune hepatitis or other autoimmune disease, uncontrolled thyroid disease, severe cardiac disease, severe renal or hepatic impairment, seizure disorders, and CNS dysfunction. Immunosuppressed transplant recipients should not receive interferons. Interferons should be used with caution in persons who have myelosuppression or who are taking myelosuppressive drugs. Preparations containing benzyl alcohol are associated with neurotoxicity, organ failure, and death in neonates and infants and therefore are contraindicated in this population. Interferons should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 

Contraindications History of autoimmune hepatitis or severe psychiatric disorders, hypersensitivity to alpha interferons... 

Hypothyroidism, a condition in which the circulating concentrations of thyroid hormones are too low, is the most prevalent thyroid disease. Primary hypothyroidism, the commonest form, is an autoimmune disease (Hashimoto s thyroiditis) often associated with goitre. Like other autoimmune diseases, it is more prevalent in women (4 per 1000) than in men (1 per 1000). Other causes include thyroidectomy, radioac tive ablation and, in some countries, iodine deficiency. Hypothyroidism can also be caused by several drugs, including lithium, interleukin-2 and interferon. Secondary hypothyroidism is a disease caused by decreased secretion of TSH by the pituitary. 

Induction of autoimmune thyroid disease with hypothyroidism or hyperthyroidism Interferon-a, interleukin-2, interferon-B, lithium, amiodarone... 

Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Alfa interferons are abortifacient in primates and should not be administered in pregnancy. Potential drug-drug interactions include increased theophylline levels and increased methadone levels. Co-administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias. 

Autoreactive tissue disorders (autoimmune diseases)2 Prednisone, cyclophosphamide, methotrexate, interferon-a and -3, azathioprine, cyclosporine, infliximab, etanercept, adalimumab Often good, variable... 

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