A collaborative approach to improving cytokine testing

Cytokine panels are important tools for investigating excessive inflammation and immune dysfunction. For more than 15 years, Seattle Children’s Hospital maintained a cytokine panel to support its participation in clinical trials. Although the hospital’s panel was originally designed to help distinguish between sepsis and cytokine release syndrome, its use evolved as providers from a variety of specialties — including immunology, rheumatology, hematology-oncology, and gastroenterology — began ordering it to assess a broader range of conditions (1,2).

Over time, it became clear that the panel wasn’t meeting the varied clinical needs it had grown to support. Moreover, the time-consuming manual testing process placed a significant burden on laboratory staff (2,3).

To manage the increasing demand and the labor-intensive nature of cytokine testing, the laboratory director at Seattle Children’s used laboratory stewardship practices to implement a triage process. The director began reviewing all cytokine orders with providers to determine which cases required rapid in-house testing (1–2 day turnaround) versus those that could be sent to a reference laboratory (approximately 1-week turnaround) (4).

Although this approach reduced in-house testing volume by about 30% over 1 year, there was still room for improvement. Most of the test requests at the hospital were for critically ill patients who required results more urgently than a send-out could provide.

For that reason, the laboratory team initiated a structured, collaborative review process with all clinical specialties ordering cytokine testing to plan for the next revision of our cytokine platform. Given our prior experience, our main goals were to make the platform more analytically efficient and clinically relevant. We describe this process here.

Step 1: Determining clinical need

To align testing with clinical priorities, the lab team began discussions with providers 2 years before switching cytokine platforms. As part of this dialogue, we developed an online survey listing the most common cytokines available across reference laboratories. The survey asked the departmental leaders to select the three cytokines most relevant to their patient populations. This was important because cytokine panels vary widely in scope, containing anywhere from five to more than 20 analytes (1–3).

This approach allowed the lab team to identify the highest-value markers across specialties. The survey revealed six cytokines of importance to the providers: IL-1beta, soluble IL-2R, IL-6, IL-8, IL-10, TNFα, and IFNγ.

In comparison, our old cytokine kit had IL-2, IL-4, IL-6, IL-8, IL-10, TNFα, IFNγ, and GM-CSF. Several of these cytokines were rarely elevated in clinical samples (IL-2, IL-4, GM-CSF), and therefore we learned from this process that a shorter panel would be more clinically relevant for our patients.

Step 2: Conducting feasibility study and evaluating methods

Based on these results, the laboratory started considering the Luminex, MesoScale Discovery, Protein Simple Ella, and Siemens Immulite platforms. All of these platforms had most of the clinically relevant cytokines. However, we’d learned from our previous panel that we also had to factor analytical complexity, cost, and faster turnaround times into our decision.

At Seattle Children’s, the laboratory has already had experience using the Immulite platform for over 10 years, and the laboratory technologists felt this was the best solution to address their goal of analytical efficiency. Therefore, all parties involved agreed that the cytokine panel available on the Siemens Immulite platform best met the goals of analytical efficiency and clinical relevance.

Although this method did not include interferon gamma (IFN-γ), the lab already offered a validated assay for CXCL9, a stable downstream marker of IFN-γ signaling. The lab team obtained reagents to perform a feasibility study, confirming the platform’s suitability.

Transitioning cytokine testing to Immulite offered multiple advantages: Compared with the previous assay, it reduced workload and hands-on time for technologists, improved accessibility through random-access testing, and offered significantly faster turnaround times that allowed providers to make better assessments of hyperinflammation cases.

Step 3: Engaging stakeholders

With provider leadership support established from the initial survey and discussions, the lab’s next step was to present the data and rationale for the new panel to the clinical teams. During departmental meetings for each specialty, lab leaders reviewed their survey findings, compared the existing and proposed cytokine panels and platforms, and outlined the expected operational and clinical benefits. These discussions allowed for transparent communication and consensus-building across specialties.

Because the cytokine assay is best suited for evaluating severe inflammation or immune dysfunction, it was critical to ensure that providers fully understood its appropriate use, strengths, and limitations (1,4). The laboratory team outlined processes for ordering the cytokine panel with a 1–2 day turnaround time for clinically urgent treatment scenarios; they explained that, because these cases needed to be reviewed by a lab fellow or director, providers must contact the laboratory immediately to expedite their request. Otherwise, the lab will offer the panel 1 day a week. The new cytokine panel was rolled out hospital-wide in December 2025.

Adoption of the new platform has also reduced the complexity associated with sending out non-urgent requests. The team decided to discontinue the send-out option and instead simply classify testing on the Immulite platform as either “urgent” or “routine.”

Outcome

The transition to the new cytokine panel has been well received. Providers are enthusiastic about improved clinical relevance and faster turnaround times, while laboratory staff appreciate the simplified workflow. Although the change was gradual — reflecting the hospital’s long history with the previous panel — it exemplified a thoughtful, collaborative approach to laboratory process improvement (4,5). Ultimately, this effort strengthened communication and improved the laboratory team’s relationships with providers from a variety of specialties who care for critically ill patients.

Lisa M. Johnson, PhD, is a clinical chemist at Seattle Children’s Hospital and an associate professor in the department of laboratory medicine and pathology at the University of Washington. +Email: [email protected]

References

1. Gallo PM, Kim J, McNerney KO, et al. Serum cytokine panels in pediatric clinical practice. J Allergy Clin Immunol 2025; doi: 10.1016/j.jaci.2024.08.030.
2. Liu C, Chu D, Kalantar-Zadeh K, et al. Cytokines: From clinical significance to quantification. Adv Sci (Weinh) 2021; doi: 10.1002/advs.202004433.
3. Knight V, Sepiashvili L. Cytokine testing and challenges for diagnostic and clinical monitoring use. J Allergy Clin Immunol 2025; doi: 10.1016/j.jaci.2024.11.025.
4. Dickerson JA, Fletcher AH, Procop G, et al. Transforming laboratory utilization review into laboratory stewardship: Guidelines by the PLUGS National Committee for Laboratory Stewardship. J Appl Lab Med 2017; doi: 10.1373/jalm.2017.023606.
5. White TE, Wong WB, Janowiak D, et al. Strategies for laboratory professionals to drive laboratory stewardship. Pract Lab Med 2021; doi: 10.1016/j.plabm.2021.e00249.