Introduction Permethrin is one of the most widely used insecticides in the United States. Previous studies have reported associations of permethrin use with increased risk of multiple myeloma (MM) and its precursor, monoclonal gammopathy of undetermined significance (MGUS). Biological mechanisms underlying these associations remain unclear, with some evidence linking permethrin to altered hematological parameters, underscoring the need to further explore immunologic markers related to permethrin exposure.

Objective Evaluate associations between recent occupational permethrin use and circulating levels of immunologic markers.

Methods We conducted a longitudinal investigation among 33 male permethrin applicators ≥50 years of age in the Biomarkers of Exposure and Effect in Agriculture study who had blood samples collected in the offseason and within a day after permethrin application (recent use); 27 of these applicators also had a sample collected ~3 weeks after permethrin use. As an external comparison, we analyzed one-time blood samples from 70 age-matched non-farming controls. Serum levels of 87 immunologic markers were assessed using a multiplex immunoassay. Multivariable linear mixed models were used to estimate associations between permethrin use and immunologic markers.

Results Among pesticide applicators, recent permethrin use (vs. offseason) was associated with increased serum caspase-8 (mean relative (fold)-change in protein concentration: 1.36; 95% confidence interval: 1.04–1.78) and arginase-1 (1.24; 1.00–1.53) and reduced pleiotrophin (–1.15; –1.26, –1.05) and matrix metalloproteinase-12 (MMP-12; –1.12; –1.26, 1.00) levels. Associations with caspase-8, arginase-1, and pleiotrophin persisted at ~3 weeks after permethrin use (vs. offseason). Compared to non-farming controls, we also observed increased caspase-8 (1.44; 1.10–1.88) and reduced MMP-12 (–1.31; –1.61, –1.06) levels among applicators after recent permethrin use, with associations persisting ~3 weeks after use.

Conclusion Although exploratory, these findings suggest that permethrin use may be associated with certain immunologic markers previously implicated in MGUS/MM pathogenesis, particularly caspase-8 and MMP-12, which are involved in apoptosis and angiogenesis, respectively.