Association of IL-1α and IL-1β polymorphisms with functional recovery following rehabilitation in Multiple Sclerosis, a pilot study

Multiple sclerosis (MS) is a chronic neuroinflammatory disorder characterized by demyelination and progressive disability. While genetic determinants of disease susceptibility and treatment response are well established, their influence on rehabilitation outcomes remains largely unexplored. Interleukin-1 (IL-1) cytokines are central regulators of neuroinflammation and may modulate recovery processes within the central nervous system.

We evaluated the association between IL-1α rs3783521 and IL-1β rs16944, rs1143627, and rs1143634 polymorphisms and rehabilitation outcomes in 162 MS patients undergoing inpatient multidisciplinary rehabilitation who did not receive disease-modifying treatments during the study period. Disability was assessed using the Expanded Disability Status Scale (EDSS) and the Modified Barthel Index (BI) at admission and discharge. Changes in disability (ΔEDSS, ΔBI) were analyzed using non-parametric tests and multivariable generalized linear models adjusted for clinical covariates. Genotype distributions were also compared with published Italian healthy control datasets.

IL-1β rs1143634 was associated with MS susceptibility, with the A allele conferring increased risk. All polymorphisms showed significant associations with ΔEDSS in univariate analyses. In adjusted models, IL-1α rs3783521 and IL-1β rs1143634 A alleles were independently associated with greater functional improvement, whereas the IL-1β rs16944 A allele was associated with poorer recovery. IL-1β rs1143627 influenced outcomes under a dominant model. No robust associations were observed for ΔBI. Notably, the combined effect of AG alleles across IL-1α rs3783521 and rs16944 identified a subgroup with the greatest improvement in disability after rehabilitation.

IL-1 genetic variability may contribute to inter-individual differences in rehabilitation response in MS. These findings support a role for neuroinflammatory genetic profiling in predicting functional recovery and advancing personalized rehabilitation strategies.