Tezepelumab Helps to Stabilize Bronchial Epithelial Immune Response to Respiratory Viruses


Though primarily observational, this research’s biggest asset is its experimental design and its exploration of viral stimulus-induced bronchial epithelial cell responses from asthmatic donors being treated with tezepelumab.

The blocking of thymic stromal lymphopoietin (TSLP) with the drug tezepelumab may help to stabilize asthma patients’ bronchial epithelial immune responses to viruses of the respiratory system, according to new findings.1

This recent research—a part of the UPSTREAM study—was conducted to examine the impact on asthma patients of blocking TSLP, specifically with regard to host resistance (IFNβ, IFNλ, and viral load). It was also conducted to look at the airway epithelial inflammatory results of viral stimulation.

The research was led by Lina Uller, from the Department of Experimental Medicine at Lund University in Lund, Sweden. Uller and colleagues explained that there had not been much exploration into the mechanisms responsible for the impact of TSLP inhibition on exacerbations of patients’ asthma, as well as the possible influence of tezepelumab on hosts’ ability to resist and to tolerate viruses.

“Based on increased understanding of the importance of inflammatory effects of viral infection for disease development, we hypothesized that blocking a major switch of T2-inflammation such as TSLP may improve host tolerance to virus stimulation,” Uller and colleagues wrote.2

Background and Findings

The investigators’ work involved the utilization of bronchial epithelial cell cultures and bronchial-alveolar lavage fluid (BALF) from subjects that reported having uncontrolled asthma and who had taken part in the double-blind, placebo-controlled UPSTREAM study. The new research was conducted to look at the effects of 12 weeks of treatment with tezepelumab—700 mg IV—on participants’ airway hyperresponsiveness and their resulting inflammation.

Baseline and post-treatment bronchoscopies were also carried out by the research team as part of their research. The team made participation in the trial contingent on subjects having had an ACQ5 score above 1, a diagnosis of asthma, and airway hyperresponsiveness to inhaled mannitol even after using several different medications.

Both current and former cigarette smokers with more than 10 ‘pack-years’ were considered to be excluded from the trial, and subjects’ oral corticosteroid or biologic use at the time of the study was not sanctioned.

Subjects’ bronchial epithelial cells (BECs) were gathered from them prior to and following their treatment, and the investigators' efforts involved assessing tezepelumab’s impact on asthma patients’ airway hyperresponsiveness and inflammation. A total of 39 individuals took part in the team’s research, with their BALF gathered and looked at in a blinded manner. The mechanistic in vitro sub-study was included in the protocol following the inclusion of 13 subjects.

This resulted in a total of 26 subjects that had BECs taken prior to and following their treatment with the drug. Specifically, 13 were in the placebo arm and 13 were in the tezepelumab arm.

The subjects’ BECs were cultured in a controlled and in vitro environment, and the BECs were exposed to either the viral infection mimic poly(I:C) or they were infected with rhinovirus (RV). The investigators conducted their assessment through the use of RT-qPCR and multiplex ELISA to measure T2- and pro-inflammatory cytokines, alarmins, IFNβ, IFNλ, and viral load both prior to and following stimulation.

Following a total of 12 weeks of tezepelumab therapy, the research team reported a notable diminishing of IL-33 expression in resting BECs. They additionally noted a decrease in subjects’ level of IL-33 protein in the BALF.

Also, the investigators found that when the BECs faced exposure to poly(I:C) in the aftermath of the drug’s administration, both the IL-33 gene and the subjects’ levels of protein indicated a decrease, despite the fact that the expression of the TSLP gene continued to not be impacted.

The drug tezepelumab also was shown to have led to a diminished release of IL-13, IL-4, and IL-17A that was induced by poly(I:C) in the BECs. Despite this, the investigators noted that the expression of both IFNβ and IFNλ, as well as the viral load, also were shown to have been unchanged.

Thus, the team concluded that with asthma, when the drug was implemented to inhibit TSLP in live subjects, this resulted in a diminished airway epithelial inflammatory reaction due to viral challenges.

The reduction included an IL-33 and T2 cytokine decrease while leaving the subjects’ antiviral defenses unimpacted from the treatment. This data led the investigators to conclude that blocking TSLP can lead to the stabilization of subjects’ bronchial epithelial immune response to respiratory viruses.

“Thus, these novel data suggest that blocking TSLP stabilizes the bronchial epithelial immune response to virus, explaining in part the effect of tezepelumab on asthma exacerbations,” they wrote.


  1. Sverrild, A., Cerps, S., Nieto-Fontarigo, JJ, et al. Tezepelumab decreases airway epithelial IL-33 and T2-inflammation in response to viral stimulation in patients with asthma. Allergy. 2023; 00: 1-11. doi:10.1111/all.15918.
  2. Uller L, Persson C. Viral induced overproduction of epithelial TSLP: role in exacerbations of asthma and COPD? J Allergy Clin Immunol. 2018; 142(2): 712.
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