Interferon-γ In Patients Research Articles

Immunologic Alterations in Schizophrenia: Neopterin, L-Kynurenine, Tryptophan and T-Cell Subsets in the Acute Stage of Illness

Abstract It is well established now that in diseases with activated cell-mediated immunity increased formation of neopterin and degradation of tryptophan is an indication of endogenous production of interferon-γ in patients. Therefore increased neopterin levels are associated with increased kynuremne levels and decreased tryptophan in patients suffering from virus infections, malignant diseases or autoimmunity. To investigate cell-mediated immunity m schizophrenia, neopterin, L-kynurenine, L-tryptophan and T-cell-subsets were measured in 10 chronic schizophrenic patients, addmitted to hospital due to acute psychiatric relapse. Low neopterin concentrations were found at the beginning of hospitalisation and followed by a significant increase at the time of discharge (p = 0.02). Mean neopterin values were still within the 95th percentile of healthy controls. Kynuremne levels showed a similar development (p = 0.03) as neopterin whereas tryptophan values were low at admission without any significant changes thereafter. CD3 + and CD4+-cells presented with highest numbers at admission, followed by a continuous decrease and NK-cells were found lowest on day 0 with a gradual increase by day 7. These findings argue against acute virus infection in acutely ill schizophrenic patients because this would be associated with incerased neopterin fromation and tryptophan dagradation, rather the data would be in line with a shift from TH-1 to TH-2-type immune reaction which which is common in chronic infections.

Decreased production of interferon-γ in patients with chronic hepatitis C treated with ribavirin in combination with interferon-alpha

Decreased production of interferon-γ in patients with chronic hepatitis C treated with ribavirin in combination with interferon-alpha

Induction of neutralizing autoantibodies to interferon-γ in patients with polyneuropathy

We previously demonstrated the induction of IFN-gamma in polyneuropathy patients associated with monoclonal gammopathy, but not in patients with presumably non-immunological types of neuropathy. We herein examined mechanism involving release of neutralizing autoantibodies (Aabs) to IFN-gamma in sera from those patients. In contrast to polyneuropathy patients with monoclonal gammopathy, patients with polyneuropathy of presumably non-immunological types showed increased production of neutralizing Aabs specific for IFN-gamma. These results demonstrate a role for autoimmunity in cytokine regulation. However, their association to the clinical manifestations of the disease requires further investigations, which are necessary for future consideration in therapeutic strategies.

Relationship between serum 3,5,3'-triiodothyronine and serum interleukin-8, interleukin-10 or interferon gamma in patients with nonthyroidal illness.

In order to further delineate the role of cytokines in the pathogenesis of the low T3 syndrome, we studied the association between serum T3 and serum interferon gamma (IFN gamma), interleukin-8 (IL-8) and interleukin-10 (IL-10) in 99 consecutive patients hospitalised because of a wide variety of nonthyroidal diseases; none used drugs affecting thyroid hormone metabolism. Patients were divided in group A (normal serum T3 and T4), group B (subnormal serum T3 and normal T4) and group C (subnormal T3 and T4). Serum IFN gamma, IL-8 and IL-10 were not different between group A, B and C (with the exception of a small increase of IFN gamma in group B). Serum T3 was slightly related to serum IL-8 (r = 0.25, p < 0.05), but not to IFN gamma and IL-10. Stepwise multiple regression indicated that these serum cytokines were not independent determinants of the variability in serum T3. The results do not support any role of circulating IFN gamma, IL-8 or IL-10 in the pathogenesis of the low T3 syndrome during illness.

Serum levels of interleukin 1α, tumour necrosis factorα and interferon-γ in patients with psoriasis vulgaris

Serum levels of interleukin 1α, tumour necrosis factorα and interferon-γ in patients with psoriasis vulgaris

Activated suppressor cells inhibit synthesis of interferonγ in patients with multiple sclerosis and normal subjects

Activated suppressor cells inhibit synthesis of interferonγ in patients with multiple sclerosis and normal subjects

Activated suppressor cells inhibit synthesis of interferonγ in patients with multiple sclerosis and normal subjects

Activated suppressor cells inhibit synthesis of interferonγ in patients with multiple sclerosis and normal subjects

A phase I trial of recombinant human interferon-γ in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS)

A Phase I study of recombinant interferon-gamma (rIFN-gamma) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-gamma. rIFN-gamma was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2-4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7-12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1-1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-gamma is given at doses at or near this MTD.

A phase I-II trial of the combination of recombinant leukocyte A interferon and recombinant human interferon-gamma in patients with metastatic malignant melanoma.

Twenty patients with advanced malignant melanoma received daily intramuscular recombinant leukocyte A interferon (rIFN-alpha A, Roferon-A, Hoffmann-Laroche, Nutley, NJ) concomitant with recombinant human interferon-gamma (rIFN-gamma Genentech, South San Francisco, CA). During the first week alpha dose was 2 X 10(6) U/m2 and the gamma dose was 0.01 mg/m2 with escalations, if clinically tolerable, during the second week to 5 X 10(6) U/m2 and 0.025 mg/m2, respectively. Twelve patients received the escalated doses; subsequent granulocytopenia and a flu-type illness were severe in four of the 12. We observed one partial response of MRI-documented and biopsy-confirmed osseous metastases for 7+ months. For all study participants, the median time to progression was 1 month with a median survival of 6 months. From the dose and schedule which we utilized, concurrent rIFN-alpha A and rIFN-gamma provided little impact on advanced malignant melanoma.