Lung Fibrosis Linked to Specific Cytokines in Systemic Sclerosis Patients

Researchers found that increased levels of Th-17 cytokines are associated with interstitial lung disease in patients with systemic sclerosis (SSc). Targeting this group of cytokines may improve lung inflammation and halt the progression of lung fibrosis.

Cytokines are small secreted proteins released by the immune system. They are cell-signaling molecules that have an effect on other cells.

The study, “Th-17 cytokines and interstitial lung involvement in systemic sclerosis,” was published in the Journal of Breath Research.

SSc has two main disease manifestations, the limited and diffuse forms, depending on the extent of the fibrosis. They are also charactized by different forms of pulmonary involvement: While limited SSc is characterized by pulmonary arterial hypertension (PAH), diffuse SSc is associated with interstitial lung disease (ILD).

The mechanisms underlying pulmonary fibrosis remain unknown, but here a team of researchers hypothesized that a particular group of cytokines could be involved.

Researchers looked at cytokines produced by a specific group of immune cells, the Th17 cells, which belong to the larger group of T-helper cells, which are capable of modulating immune system responses. Many cytokines, such as TGF-beta, are important for the formation of Th17 cells, but they are also responsible for fibrosis development in the lungs. Therefore, researchers hypothesized that the process for Th17 formation could play a role in interstitial lung disease in SSc patients.

To test their hypothesis, researchers measured the levels of Th17-related cytokines (IL1-beta, IL-6, IL-17, IL-21, IL-22, IL-23, TGF-beta) in exhaled breath condensate (EBC) and in serum collected from SSc patients and a group of healthy controls. The team also measured the levels of proinflammatory (TNF-alpha) and anti-inflammatory (IL-10) in both groups.

A total of 29 patients with SSc (28 females and one male) were enrolled in the study; the control group included 20 healthy subjects (12 females and eight males). Patients were divided into two subgroups according to the limited (17 patients) or diffuse (12 patients) cutaneous distribution of the disease.

Researchers found that in both limited and diffuse types of SSc, the EBC levels of all cytokines and the majority of cytokines in serum showed significantly higher levels in patients when compared to controls. When researchers analyzed Th-17 cytokines, they found that EBC levels and serum levels of IL-10 and TNF-alpha were significantly higher in diffuse compared to limited SSc.

Importantly, they observed that the interstitial lung disease score was significantly associated with the EBC levels of IL1-beta and with the serum IL-23, TNF-alpha and IL-10 levels.

Pulmonary function tests, such as lung carbon monoxide diffusing capacity, showed a negative correlation with EBC levels of IL1-beta, IL-17 and serum IL-10.

Overall, these results show a link between higher levels of Th-17 cytokines in EBC and serum of systemic sclerosis patients with interstitial lung involvement.

Targeting these type of cytokines could represent a potential therapeutic strategy for lung fibrosis in these patients.