Autoimmune inflammation can elevate serum 1,25-dihydroxy vitamin D
Autoimmune inflammation, though a pervasive scourge, seems to often elude diagnosis. I have found that patients with an autoimmune component to their case often have elevated 1,25-dihydroxy vitamin D (calcitriol). This is not the 25-hydroxy vitamin D3 (cholecalciferol metabolite) that we always test to determine vitamin D3 sufficiency. Often with normal and even low vitamin D3 levels, patients with various degrees of active autoimmunity are testing for elevated 1,25-dihydroxy vitamin D levels. Now research published in PLOS One (Public Library of Science) shows how autoimmune inflammation and elevated 1,25-dihydroxy vitamin D are associated. The authors sought to elucidate the mechanism by which 1,25-Dihydroxyvitamin D3 suppresses autoimmune inflammation:
"1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) suppresses autoimmunity and inflammation; however, the mechanism of its action has not been fully understood. We sought in this study to determine whether the anti-immune/anti-inflammatory action of 1,25(OH)2D3 is in part mediated through an interplay between 1,25(OH)2D3 and toll-like receptor (TLR)7/8 signaling."
To do so they used experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis, and found that...
"1,25(OH)2D3 treatment prior to and/or following experimental autoimmune encephalomyelitis (EAE) induction effectively reduced inflammatory cytokine expression in the spinal cord and ameliorated EAE. These effects were accompanied with a reduction in expression of several TLRs with the most profound effect observed for TLR8. The expression of TLR8 adaptor protein MyD88 was also significantly reduced by 1,25(OH)2D3."
Moreover, 1,25(OH)2D3 also reduced the inflammatory expression of monocytes (white blood cells that becomes activated as macrophages:
"1,25(OH)2D3 treatment not only significantly reduced TLR8 expression but also the expression or activity of MyD88, IRF-4, IRF-7 and NF-kB in monocytes challenged with TLR8 ligands."
Bear in mind that NF-kB is a 'final common pathway' for inflammation in autoimmunity. And regarding the clinically important pro-inflammatory cytokines TNF-α and IL-1β:
"As a result of inhibition on TLR8 signaling cascade at various stages, 1,25(OH)2D3 significantly diminished the TLR8 target gene expression (TNF-α and IL-1β)."
In their conclusion the authors focus on the implied mechanism for the anti-inflammatory effects of 1,25(OH)2D3:
"In summary, our novel findings suggest that TLR8 is a new target of 1,25(OH)2D3 and may mediate the anti-inflammatory action of 1,25(OH)2D3. Our findings also point to a destructive role of TLR8 in EAE and shed lights on pathogenesis of multiple sclerosis."
Clinical note: If you've read this far you probably know how I felt on seeing this, considering all the patients I'm seeing with elevated lab results for 1,25(OH)2D3. In a personal e-mail communication the corresponding author Xuezhong Qin, Ph.D., Associate Professor in the Division of Regenerative Medicine at Loma Linda University School of Medicine states:
"Serum 1,25D is frequently elevated in patients with autoimmune inflammatory diseases such as IBD. It is likely this is caused by activated macrophages which express [a] high level of CYP27b1."
I encourage clinicians to measure 1,25-dihydroxy vitamin D (calcitriol) in their patients for whom autoimmunity seems likely as a meaningful metric for case management and to add to the body of knowledge on autoimmune inflammation.