Smoking Linked to Inflammation and Increased Disease Activity in SLE

Smoking was associated with an increase in B cell-activating factor (BAFF), arthritis, migraine (lupus headache), and Raynaud’s phenomenon, along with a decrease in interferon-gamma (IFN-γ) levels in patients with systemic lupus erythematosus (SLE), according to a study published in Lupus Science & Medicine.¹

“Cigarette smoke exposes the epithelial cells of the larynx, bronchi and lung to more than 60 chemical carcinogens, which each has the potential to cause DNA damage.Furthermore, smoking has been shown to increase and decrease many proinflammatory and anti-inflammatory cytokines in the general population,” investigators stated. “Yet, there are (very) limited data on the impact of smoking on serum cytokines in patients with SLE, especially in the context of medication use and organ damage.”

This cross-sectional study examined 99 patients with SLE to understand the effects of smoking on SLE. To determine the impact of current smoking status, smoking was defined as current consumption. Ex-smokers (median 10 years) were placed in the non-smoking group.

During each appointment, serological, immunological, and biochemistry levels were collected, including IFN-γ, interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12, IL-17, BAFF, macrophage inflammatory protein 1 alpha (MIP-1α; patients with SLE), MIP-1β (patients with SLE), monocyte chemoattractant protein 1, and tumor necrosis factor-alpha (TNF-α). Clinical data, such as disease activity was determined using the SLE Disease Activity Index-2K (SLEDAI-2K). Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index for SLE (SDI) and Lupus Low Disease Activity State (LLDAS) was recorded over time. Medications, including prednisone, cytostatic agents, and immunomodulators were noted.

Linear regression models adjusted for age, sex, and clinical characteristics.

The average age for patients in the SLE cohort was 48 years, 86.9% were female, and the mean disease duration was 10 years. A total of 35 patients (35.4%) were current smokers, with an average of 7 cigarettes per day for an average period of 24 years. Within the non-smoker group, 25 (39.1%) were ex-smokers. Both current and non-smokers had similar burdens of comorbid vascular, pulmonary, malignancy, and metabolic pathology, as well as total SDI scores and damage. However, those with smoking exposure had higher accrued damage (69.0% vs 46.3%) and malignancy (20.7% vs 4.9%).

Migraine (OR 2.82, 95% CI 1.07 to 7.44), Raynaud’s phenomenon (OR 5.15, 95% CI 1.95 to 13.56), which was higher in male patients, non-steroidal anti-inflammatory drug (NSAID) use (OR 6.88, 95% CI 1.99 to 23.72), and arthritis (OR 3.19, 95% CI 1.19 to 8.60) were more frequently seen in smokers when compared with non-smokers. SLEDAI-2K scores were similar regardless of smoking status. Global disease activity (GDA) visual analogue scare (VAS) scores were higher in those who were current smokers.

Smoking increased the risk of developing malar rash (OR 3.40, 95% CI 1.23 to 9.34) and mucosal ulcers (OR 3.31, 95% CI 1.36 to 8.05). While smokers had similar immunological disease activity when compared with non-smokers, hemoglobin, B cells, and mean corpuscular volume (MCV) levels were higher in this patient population. Medications were similar regardless of smoking status except for the additional use of NSAIDs in smokers.

Patients with SLE had higher levels of BAFF and MCP-1 when compared with controls (1.74 vs 0.94 ng/mL, p<0.001; 137.42 vs 98.22 pg/mL, p=0.028, respectively). Further, the SLE cohort had lower levels of IL-1β and TGF-β1 (26.85 vs 67.86, p<0.001; 581.74 vs 733.39, p=0.018, respectively).

Within the SLE cohort, BAFF levels were higher (2.01 vs 1.61 ng/mL, p=0.034), yet IFN-γ and TNF-α levels were lower in patients who were current smokers when compared with those who did not smoke (39.37 vs 82.98 pg/mL, p=0.002; 35.41 vs 58.37 pg/mL, p=0.024, respectively).

After adjustments, smoking increased BAFF by 27% and decreased IFN-γ levels by 42%.

A large range of disease characteristics and adjustment for cytokines strengthened the study. However, all patients were of Northern European descent and had relatively low disease activity, which limits generalizability. Additionally, any smoking exposure was self-reported. Lastly, as results were based on clinical and serological findings, investigators could not confirm the effects of smoking on BAFF, IFN-γ, and IL-1β.

“Smoking cessation should be encouraged in SLE with the aim to reduce systemic inflammation (BAFF and physician GDA), arthritis, vasospasticity, cutaneous features, and NSAID requirement, while improving medication efficacy (hydroxychloroquine) and innate immune competence (IFN-γ),” investigators concluded.

Reference:

Raymond WD, Hamdorf M, Furfaro M, Eilertsen GO, Nossent JC. Smoking associates with increased BAFF and decreased interferon-γ levels in patients with systemic lupus erythematosus. Lupus Sci Med. 2021;8(1):e000537. doi:10.1136/lupus-2021-000537