Immune reactions interferons

Patients with a variety of cancers and some viral diseases excrete relatively large amounts of neopterin, formed by dephosphorylation and oxidation of dihydroneopterin triphosphate, an intermediate in biopterin synthesis. This reflects the induction of GTP cyclohydrolase by interferon-y and tumor necrosis factor-a in response to the increased requirement for tetrahydrobiopterin for nitric oxide synthesis (Section 10.4.2). It is thus a marker of ceU-mediated immune reactions and permits monitoring of disease progression (Werner et al., 1993,1998 Berdowska and Zwirska-Korczala, 2001). 

Only an efficient antiyiral immune reaction can eliminate the hepatitis C virus. In cases of acute HCV infection, minimal (endogenous) interferon-a values are detectable in the serum, i.e. the virus effects a poor interferon induction in the organism. The CD8+ and CD4 T lymphocytes appear to be mainly responsible for virus elimination. The problems of HCV infection lie in the fact that the patient has virtually no chance of spontaneous improvement or even healing with a chronic course of disease, i.e. there is practically no self-limiting factor in a disease process that has become chronic. 

The early impression that interferon alfa, alone or in combination with ribavirin, could reactivate or cause new subcutaneous sarcoid nodules and pulmonary or generalized sarcoidosis, has been confirmed by several reports, with prompt recovery after interferon alfa withdrawal (SED-13, 1097) (SEDA-20, 330) (SEDA-22, 404). The incidence may have been underestimated in one series, 3 patients out of 60 who received interferon alfa alone or combined with ribavirin developed pulmonary sarcoidosis (351). In a review of 27 cases, the time to onset was 15 days to 30 months, and there were dermatological signs in 50% (352). Five patients had also taken ribavirin, but an enhanced T cell immune reaction from the combination of interferon alfa plus ribavirin is speculative. However, the association of cutaneous or systemic sarcoidosis with interferon alfa, alone or in association with ribavirin, has been exemplified by various reports (353,354), including one patient whose sarcoidosis resolved with prednisone despite continued interferon alfa treatment (355). 

The so-called resistant strains, however, show a different response to mercury exposure. These resistant strains also show an increase in MHC expression molecules on B-cells, but this response is extremely short-lived, and increases in serum IgE were not observed (Dubey et al. 1991a Prouvost-Danon et al. 1981). The difference in the responses of the so-called resistant and susceptible strains may be found in the activation of Thl cells and the increase in secretion of -interferon by the Thl cells of resistant animals (van der Meide et al. 1993). The susceptible strains do not show an increase in -interferon production with mercury exposure. Because -interferon inhibits the proliferation of Th2 cells, the absence of this response in the susceptible strains may allow the Th2 cell-stimulated production of autoantibodies to occur, whereas in the resistant strains the production of antibodies is curtailed. Thus, differences in the activation of Thl versus Th2 cells may underlie the differences in susceptibility of various individuals. Studies using in-bred strains of mice and rats have determined that the susceptibility to the different immune reactions is governed by both MHC genes as well as other genes (Aten et al. 

Formulation interferon has anti-dysimmune and anti-viral actions. Some dysimmune diseases are known to be caused by a persistent immune reaction to a viral, bacterial, or other infection, and most or all of them are suspected to be of that pathogenesis. 

Passive immunization consists of transfer of immunity to a host using preformed immunologic products. From a practical standpoint, only immunoglobulins have been used for passive immunization, since passive administration of cellular components of the immune system has been technically difficult and associated with graft-versus-host reactions. Products of the cellular immune system (eg, interferons) have also been used in the therapy of a wide variety of hematologic and infectious diseases (see Chapter 56). 

Hypothyroidism occurs more often than hyperthyroidism, and spontaneous resolution is expected in almost 60% of patients with or without interferon alfa withdrawal. Finally, female sex and the presence of baseline thyroid autoimmunity were confirmed to be the most significant risk factors. The mechanisms of interferon alfa-induced thyroid dysfunction are not yet fully clarified. Although an autoimmune reaction or immune dys-regulation are the most likely mechanisms, a direct inhibitory effect of interferon alfa on thyrocytes should be considered in patients without thyroid antibodies. 

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