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Antibodies against interferon (IFN) could explain the lack of response to treatment or the development of autoimmune processes. The albumin content and the freeze-drying process of IFN alpha formulations could be involved in the generation of such antibodies in treated patients. To study this, the immunogenicity of four formulations of human recombinant IFN alfa-2b was compared in mice. One-hundred sixty Balb/c mice were randomly and evenly distributed among the following four formulations: Heberon Alpha R, lyophilized containing 1.5 mg albumin per 3 x 10 6 IU of IFN, lyophilized albumin-free, or liquid albumin-free, and Reaferon-ES, lyophilized with 5 mg albumin per 3 x 10 6 IU of IFN. They were immunized subcutaneously with 100 000 IU of IFN alpha-2 b three times a week for four weeks. Mice immunized with Reaferon-ES produced the highest serum titers of IFN alpha-2b antibodies by ELISA in the last 2 weeks, while the Heberon Alpha R liquid albumin-free formulation was the least immunogenic. Intermediate titers were obtained with the Heberon Alpha R lyophilized formulations, although they were larger for the formulation with albumin. We can conclude that albumin content and the freeze-drying process seem to have an influence on the formation of antibodies in mice. [ABSTRACT FROM AUTHOR]

El interferón gamma (IFNγ) es una citocina de tipo Th1. El estudio del sistema del IFNγ y su receptor es esencial para el empleo terapéutico más eficaz de esta molécula. Se identificaron diferentes formas moleculares del IFNGR1entre 84 y 13 kDa, y el receptor soluble (60 a 67 kDa) como consecuencia de procesamientos proteolíticos , con capacidad de unir al IFNγ. Se describe una nueva forma de interacción entre los receptores para IFNα e IFNγ, dependiente de la presencia de IFNα. El IFNGR1 soluble en el plasma de pacientes con artritis reumatoide (AR) es superior al de los controles. El IFNγ modula de manera negativa el CCR-4, un receptor de quimiocina elevado de manera significativa en pacientes con artritis reumatoide juvenil (ARJ). Se desarrolló un antagonista anti-IL-2-IFNγ recombinante, que inhibe las acciones biológicas de IL-2 e IFNγ, y convierte esta proteína en un antagonista de tipo Th1 (AnTh1), con un gran potencial para el tratamiento de enfermedades autoinmunes. [ABSTRACT FROM AUTHOR]

Interferon gamma (IFNγ) is a Th1-type cytokine. The study of the IFNγ system and its receptor is essential for increasing the efficacy of this drug for clinical settings. Here we describe the role of IFNγ and its receptor on the physiopathology of disorders involving the immune system. Several molecular forms of IFNGR1, from 84 to 13 kDa, and soluble receptor (60-67 kDa) with the capacity to bind IFNγ arising from proteolytic processing events are shown. These forms bind IFNγ. A new type of interaction between the IFNα and IFNγ receptors that depends on the presence of IFNα is also described. There are high levels of soluble IFNGR1 in the plasma of rheumatoid arthritis (RA) patients. The role of IFNγ as a negative modulator for CCR-4, a chemokine receptor up-regulated significantly in juvenile rheumatoid arthritis (JRA) patients, is described. A recombinant anti-IL-2-IFNγ antagonist was developed. This molecule inhibits the biological actions of IL-2 and IFNγ, turning this protein into a Th1 antagonist (AnTh1) potentially useful for the treatment of autoimmune disorders. [ABSTRACT FROM AUTHOR]