Changes in lung immune cells related to clinical outcome during
treatment with infliximab for sarcoidosis
Background: Pulmonary sarcoidosis is characterized by an exaggerated
CD4+ T-cell response and formation of non-necrotizing granulomas. Tumour
necrosis factor α (TNF-α) is regarded as crucial for granuloma formation
and TNF-α inhibitors offer a 3rd line treatment option for patients not
responding to conventional treatment. However, not all patients benefit
from treatment, and an optimal dose and treatment duration have not been
established. Insight into the influence of TNF-α inhibitors on lung
immune cells may provide clues to what drives inflammation in
sarcoidosis and improve our understanding of treatment outcomes.
Objectives: To evaluate effects of treatment with the TNF- α inhibitor
infliximab on lung immune cells and clinical features of the patients.
Methods: Thirteen patients with sarcoidosis refractory to conventional
treatment were assessed with bronchoalveolar lavage (BAL), spirometry
and CT scan in close adjacent to start of infliximab treatment. These
investigations were repeated after six months of treatment. Results:
Treatment with TNF- α inhibitor infliximab was well tolerated with no
adverse events, except for one patient who developed a probable adverse
event with liver toxicity. Ten patients were classified as responders,
having a reduced CD4/CD8 ratio, a decreased percentage of CD4+ T-cells
expressing the activation marker CD69 and number of mast cells
(p<0.05 for all). The percentage of T regulatory cells
(Tregs), defined as FoxP3+ CD4+ T-cells decreased in most patients.
Conclusions: Six months of infliximab treatment in patients with
sarcoidosis led to signs of decreased CD4+ T-cell alveolitis and
decreased mastocytosis in the lungs of responders.