IL-18 gene polymorphisms affect IL-18 production capability by monocytes

Area of Science:

• Immunogenetics
• Molecular Biology
• Respiratory Medicine

Background:

• Interleukin-18 (IL-18) is a pro-inflammatory cytokine implicated in asthma pathogenesis.
• Previous research established a link between IL-18 gene polymorphism 105A/C and asthma.
• The functional consequence of IL-18 gene polymorphisms on IL-18 production remains to be fully elucidated.

Purpose of the Study:

• To investigate the relationship between IL-18 gene polymorphisms and the IL-18 production capacity of human monocytes.
• To determine the impact of specific IL-18 gene polymorphisms (105A/C and -137G/C) on monocyte-derived IL-18 levels.

Main Methods:

• Genotyping of IL-18 gene polymorphisms (105A/C and -137G/C) using Polymerase Chain Reaction (PCR).
• Quantification of IL-18 production by monocytes, stimulated ex vivo with lipopolysaccharide (LPS) or calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (PMA), measured via Enzyme-Linked Immunosorbent Assay (ELISA).

Main Results:

• Monocytes from individuals with the IL-18 105A/A genotype exhibited significantly higher spontaneous and stimulated IL-18 production compared to those with the 105A/C genotype.
• Similarly, monocytes from individuals with the -137G/G genotype showed significantly greater IL-18 production than those with the -137G/C genotype.
• Significant linkage disequilibrium was observed between the IL-18-105A/C and -137G/C polymorphisms.

Conclusions:

• Specific IL-18 gene polymorphisms (105A/A and -137G/G) are associated with an enhanced capacity for IL-18 production by monocytes.
• This increased genetic capacity to produce IL-18 in response to stimuli may contribute to the susceptibility and onset of asthma.