Wednesday, 14 Nov 2018

You are here

IL-12 and IL-23 Promote Giant Cell Arteritis

It has been postulated that TH1 and TH17 pathways are implicated in the pathogenesis of giant cell arteritis (GCA); this is supported by new research showing that interleukin 12 (IL-12) and interleukin 23 (IL-23) may stimulate inflammatory and proliferative pathways relevant to the pathogenesis of GCA.

Temporal artery biopsy (TABs) explants and peripheral blood mononuclear cells (PBMC) were studied in culture and for gene expression. 

TABs showed increased expression of interleukin 12p35 (IL-12p35) and interleukin 23p19 (IL-23p19) in temporal artery (TA) biopsy-positive patients. 

IL-12p35 TA expression was significantly increased in those with cranial ischemic complications (p=0.026) and large vessel vasculitis (p=0.006).

IL-23p19 TA expression was increased in those with two or more relapses (p=0.007).

In cultures, exogenous IL-12 significantly increased interleukin 6 (IL-6) (p=0.009), interleukin 22 (IL-22) (p=0.003) and interferon γ (IFN-γ) (p=0.0001) and decreased interleukin 8 (IL-8) (p=0.0006) secretion.

Exogenous IL-23 significantly increased IL-6 (p=0.029), IL-22 (p=0.001), interleukin 17A (IL-17A) (p=0.0003) and interleukin 17F (IL-17F) (p=0.012) secretion.

In ex vivo TA explants, IL-23 significantly increased gene expression of IL-8 (p=0.0001) and CCL-20 (p=0.027) and protein expression of IL-6 (p=0.002) and IL-8 (p=0.004). IL-12 (p=0.0005) and IL-23 (p<0.0001) stimulation increased the quantity of myofibroblast outgrowths from TABs.

IL-12 and IL-23 play important roles in promoting Th1 and Th17 pathway inflammation and in amplifying proinflammatory cytokine signaling. 

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

Scleroderma Expert Treatment Preferences

Frustration may be the word that best characterizes many scleroderma management plans - owing to a lack of trials, lack of agreement and lack of clear guidance on management.

A panel of concerned experts  on systemic sclerosis (SSc) set out to develop consensus on SSc treatment algorithms.

IgG4-Related Disease: First Draft Criteria Presented at ACR 2018

As Dr. John Stone, MD, MPH recounted in his presentation regarding the new ACR/EULAR Classification Criteria for IgG4-Related Disease (IgG4-RD), only 15 years prior, IgG4-related disease was an unknown entity in the medical community.

Update on Myositis

The ACR/ARHP 2018 national meeting in Chicago presented us with opportunities to learn more about inflammatory myositis. A particularly interesting lecture was HOT topics in myositis. There were a few abstracts on MDA-5 related disease and a few on new or repurposed medications for dermatomyositis which will be covered here.

Checkpoint Inhibitor-related Myositis – Something Different

As expected, this year’s ACR meeting saw an upswing in the number of abstracts on immune related adverse events from checkpoint inhibitor therapy compared to last year. With the increase in approved indications for checkpoint inhibitors (CPIs), rheumatologists everywhere are going to be getting referrals for rheumatic irAEs.

Hydroxychloroquine Dosing: the Great Debate

Rheumatologists tend to be a conservative bunch of people. We’re law abiding and we (mostly) follow guidelines. Which is fine when they are in the best interests of our patients, but what do we do when we fundamentally disagree?