Caffeine intake linked to less severe lupus

Caffeine may protect against lupus according to researchers who found an inverse relationship between caffeine consumption and SLE disease activity.

People with SLE who consumed higher levels of caffeine – the equivalent of two to three cups of coffee per day – had significantly lower levels of disease activity as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) – compared to people with a low intake of caffeine, according to a study conducted at the Lupus Clinic, Sapienza University of Rome.

The study, based on prospective caffeine intake questionnaires for 89 patients with lupus – also found that the apparently protective effect of caffeine was mirrored by an inverse relationship between caffeine and inflammatory cytokine levels.

Conversely, a low caffeine intake was associated with more frequent major organ involvement – such as renal and neuropsychiatric manifestations – and anti-dsDNA positivity.

The findings – from the first reported investigation into caffeine and lupus activity – are likely explained by the effects of caffeine to down-regulate mRNA levels of key inflammation-related genes in peripheral blood mononuclear cells (PBMCs), and reduce levels of interferons and interleukins, the study investigators said.

Caffeine could also have more general anti-inflammatory effects as an inhibitor of the phosphodiesterase pathways to increase  intracellular cAMP and activate protein kinase A.

“By using this mechanism, caffeine could interact with different components of the immune system, suppressing the release of proinflammatory cytokines, influencing the activity of macrophages and natural killer cells, reducing T and B cells proliferation and, ultimately, antibodies production, they wrote in Lupus journal

In the study, a significant  inverse correlation was between both SLEDAI-2K values and levels of levels of IL-6, IL-10, IL-17, IL-27, IFNc , IFNa  and BLyS as measured by blood sampling, with increasing levels of caffeine consumption over seven day period: <29.1 mg/day (group 1), 29.2–153.7 mg/day (group 2), 153.8–376.5 mg/day (group 3) and  >376.6 mg/day (group 4).

Patients with little or no caffeine consumption (group 1) also showed more frequent lupus nephritis (37.5% vs 11.1%) and neuropsychiatric manifestations (25.0% vs  11.1%) than those with the highest caffeine consumption (group 4).

The study authors said the findings supported the hypothesis that cytokines such as IFN alpha are implicated in SLE pathogenesis: via defective immune regulation and uncontrolled lymphocyte activation as well as in increased antigen-presenting cell maturation, expansion of local immune response and tissue infiltration. Similarly a pathogenic role of IL-6 and IL-17 in SLE might be mediated by caffeine, they said.

“Thus, we could speculate that, through the modulation of serum cytokine levels, caffeine could influence disease activity and phenotype. In our cohort, patients with a low caffeine consumption showed a more severe disease phenotype, characterised by renal and neuropsychiatric involvement,” they concluded.

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