Good question, because not all anti inflammatories drugs are the same. A typical example of how the MOA is unclear yet we have been using it for such a long time!!! Are you sure all the steroids have the same MOA? For example, can you tell me which steroid is better for a patient with bacteria sepsis, high IL6, IL8, TGF-b etc.. compare to a patient with Viral sepsis (high IFNs + others)?

When I look in the macrophages, only in very recent papers that I could find the effect of steroid on M1 -> M2 macrophages. Remember MSCs can do the same thing AND in the Covid-19 study, as well as sr-GVHD, MSCs seem to be able to achieve similar result to steroid BUT using a different pathway. Thus, steroid and MSCs synergise in the ARDS study.

I have no doubt steroid could dampen inflammation. But what is the effect of steroid on other cells in the body? Also it doesn't have other effects like wound-healing, angiogenesis, anti-apoptotic, and of course the paracrine effects that MSCs have.

If you question our understanding of MSC and its MOA. I agree that there is a lot we don't know. But I can ask the same question with steroids and many other drugs and you wouldn't be able to give me an answer. most drugs (including MSCs) are not like antibody, or receptor inhibitors, which have a singular mode of action.

Steroid treatment promotes an M2 anti-inflammatory macrophage phenotype in childhood lupus nephritis

Background: M1-type proinflammatory macrophages (MΦ) promote glomerular injury in lupus nephritis (LN). However, whether this phenotype is altered by steroid therapy is unclear. Therefore, we investigated the effect of steroid treatment on MΦ phenotype in LN.

Methods: Patients with LN (7-18 years old) were divided into 2 groups: those with no treatment (N) before biopsy (n = 17) and those who underwent steroid (S) treatment (3-73 days) before biopsy (n = 15). MΦ number and phenotype were assessed by immunofluorescence. In vitro studies used monocyte-derived MΦ from healthy volunteers.

Results: Age at biopsy, urine findings, and kidney function (eGFR) were comparable between the two groups. Biopsies in N group had higher levels of active lesions such as endocapillary hypercellularity, necrosis, and cellular crescent formation (p < 0.05). The total CD68+ MΦ infiltrate was comparable between N and S groups. However, N group had more M1 MΦ (CD68+ CD86+ cells) (p < 0.05) and fewer M2 MΦ (CD68+ CD163+ cells) (p < 0.05), giving a 6-fold increase in the M2/M1 ratio in S vs. N groups. Dexamethasone treatment of cultured MΦ induced upregulation of CD163 expression, increased production of anti-inflammatory (IL-10, IL-19) and profibrotic factors (FGF-22, PDGF), and upregulated the scavenger receptor, stabilin-1. Upregulation of stabilin-1 in CD163+ M2 MΦ was confirmed in biopsies from S group.

Conclusions: Initial steroid treatment induces MΦ phenotypic change from proinflammatory M1 to anti-inflammatory or profibrotic M2 in LN with acute/active lesions. Although steroid treatment is effective for resolution of M1-medated injury, promotion of fibrotic lesions via M2 MΦ is a potential downside of steroid single therapy in LN.