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Modulating Effects of Intravenous Immunoglobulins on Serum Cytokine Levels in Patients with Primary Hypogammaglobulinemia

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Abstract

Background

Intravenous immunoglobulins (IVIG) have usually been administered for replacement therapy of humoral immunodeficiencies, but their use in treating other disorders with an immune pathogenesis is increasing. The exact mechanism of action by which IVIG are of benefit in such diseases is complex and only partly understood. One of the proposed mechanisms of action is the modulation of cytokine release.

Methods

We selected 29 patients with primary hypogammaglobulinemia (common variable immunodeficiency), receiving long-term substitutive therapy with IVIG, and 14 healthy blood donors as a control group. Blood samples were then taken before and 1 hour after finishing the IVIG infusion. Only one blood sample was obtained from the healthy controls. The cytokines studied were interleukin (IL)-1β, IL-1 receptor antagonist (IL-IRa), IL-2, IL-6, IL-8, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ.

Results

Patients with primary hypogammaglobulinemia showed significantly higher serum levels of IL-6, IL-8, IL-IRa, and TNFα than healthy controls. IVIG infusion significantly increased serum concentration levels of IL-6, IL-8, IL-IRa, and TNFα. No significant variation was observed in serum levels of IL-β, IFNγ, or IL-2 after IVIG infusion. Age, IVIG commercial preparation, and IVIG dose did not influence cytokine serum levels. Moreover, a significant correlation was observed between serum level variations of IL-IRa and TNFα, as well as an associative trend between maximum changes in IL-6 and IL-8 concentrations.

Conclusions

IVIG administration significantly alters the serum pattern of selected cytokines, which might explain, at least in part, the mechanism of action of IVIG in autoimmune or inflammatory disorders.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement

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Acknowledgments

The authors have no conflicts of interest that are directly relevant to the contents of this manuscript. This study was financed by grants from Grifols Laboratories SA (Barcelona, Spain) and RedRespira (ISCiii RTYC-CO3/11). The authors wish to thank Emilia Mur and Sara Lopez, outpatient nurses, for their kind assistance and collaboration in this research work.

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Authors and Affiliations

  1. Department of Pharmacy, Hospital Vall d’Hebron, Barcelona, Spain

    Cristina Ibáñez, Pilar Suñé, Ana Fierro &  José-Bruno Montoro

  2. Department of Biochemistry, Hospital Vall d’Hebron, Barcelona, Spain

    Santiago Rodríguez

  3. Grifols Laboratories, Barcelona, Spain

    Maite López

  4. Department of Pneumology, Hospital Vall d’Hebron, Barcelona, Spain

    Antonio Álvarez & Javier De Gracia

  5. Servicio de Farmacia, Hospital General Vall d’Hebron, Passeig Vall d’Hebron, Barcelona, 119-129, 08035, Spain

    José-Bruno Montoro

Authors
  1. Cristina Ibáñez
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  2. Pilar Suñé
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  3. Ana Fierro
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  4. Santiago Rodríguez
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  5. Maite López
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  6. Antonio Álvarez
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  7. Javier De Gracia
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  8. José-Bruno Montoro
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Correspondence to José-Bruno Montoro.

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Ibáñez, C., Suñé, P., Fierro, A. et al. Modulating Effects of Intravenous Immunoglobulins on Serum Cytokine Levels in Patients with Primary Hypogammaglobulinemia. BioDrugs 19, 59–65 (2005). https://doi.org/10.2165/00063030-200519010-00007

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