Potential Risks Related to Modulating Interleukin-13 and Interleukin-4 Signalling: A Systematic Review

Area of Science:

• Immunology
• Pharmacology
• Biotechnology

Background:

• Interleukin-13 (IL-13) and Interleukin-4 (IL-4) are type-II cytokines with overlapping functions in type-II-driven diseases like asthma and atopic dermatitis.
• These cytokines signal through a shared receptor, making them key targets for novel biologic therapies.

Purpose of the Study:

• To systematically review preclinical evidence for safety concerns associated with blocking IL-13 alone or in combination with IL-4.
• To assess potential risks related to infection, malignancy, and cardiovascular events.

Main Methods:

• A systematic literature search of BIOSIS, MEDLINE, and EMBASE databases for preclinical studies (2006-2016) on IL-13/IL-4 blockade.
• Included a search for clinical trials targeting these pathways to provide clinical context.
• Data from preclinical and clinical studies were descriptively analyzed.

Main Results:

• Preclinical studies showed expected impairment of host responses to helminth infections upon IL-13/IL-4 inhibition.
• No other preclinical safety risks regarding infection, malignancy, or cardiovascular events were identified.
• Clinical trials provided no evidence of serious safety concerns, such as increased risks for infections, malignancy, or cardiovascular events.

Conclusions:

• The preclinical and clinical data suggest that therapeutic modulation of IL-13 or IL-13/IL-4 pathways is generally safe.
• However, ongoing long-term safety assessments are necessary for biologics targeting these pathways currently in development.