Anti-Inflammatory and Immunomodulatory Effect of High-Dose Immunoglobulins in Children: From Approved Indications to Off-Label Use

Cells. 2023 Oct 7;12(19):2417. doi: 10.3390/cells12192417.

Abstract

Background: The large-scale utilization of immunoglobulins in patients with inborn errors of immunity (IEIs) since 1952 prompted the discovery of their key role at high doses as immunomodulatory and anti-inflammatory therapy, in the treatment of IEI-related immune dysregulation disorders, according to labelled and off-label indications. Recent years have been dominated by a progressive imbalance between the gradual but constant increase in the use of immunoglobulins and their availability, exacerbated by the SARS-CoV-2 pandemic.

Objectives: To provide pragmatic indications for a need-based application of high-dose immunoglobulins in the pediatric context.

Sources: A literature search was performed using PubMed, from inception until 1st August 2023, including the following keywords: anti-inflammatory; children; high dose gammaglobulin; high dose immunoglobulin; immune dysregulation; immunomodulation; immunomodulatory; inflammation; intravenous gammaglobulin; intravenous immunoglobulin; off-label; pediatric; subcutaneous gammaglobulin; subcutaneous immunoglobulin. All article types were considered.

Implications: In the light of the current imbalance between gammaglobulins' demand and availability, this review advocates the urgency of a more conscious utilization of this medical product, giving indications about benefits, risks, cost-effectiveness, and administration routes of high-dose immunoglobulins in children with hematologic, neurologic, and inflammatory immune dysregulation disorders, prompting further research towards a responsible employment of gammaglobulins and improving the therapeutical decisional process.

Keywords: anti-inflammatory; children; high dose immunoglobulin; immune dysregulation; immunomodulation; immunomodulatory; inflammation; intravenous immunoglobulin; off-label; pediatric.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Child
  • Humans
  • Immunoglobulins, Intravenous* / therapeutic use
  • Immunomodulation
  • Off-Label Use*
  • SARS-CoV-2

Substances

  • Immunoglobulins, Intravenous
  • Anti-Inflammatory Agents

Grants and funding

APC was funded by Bando F. CARISBO U-GOV: 2021_CARISBORMT_PESSION_A.