Elicit: Adalimumab and Inflammatory Pathways
Adalimumab inflammatory signaling pathways
Adalimumab modulates NF-κB, JAK/STAT, TNFα-TGFβ, Notch-1, IL-17, and IL-12/23 signaling pathways through direct TNF-α blockade, with pathway-specific effects varying by cell type, disease context, and treatment duration, mediated by coordinated changes in gene expression, protein levels, and microRNA regulation.
Abstract
Adalimumab modulates multiple interconnected inflammatory signaling pathways through direct TNF-α blockade and subsequent downstream effects. In keratinocytes, adalimumab primarily targets NF-κB signaling by downregulating IKBKB, IRAK1, TRAF2, MAP3K7, and TNFAIP3, with IKBKB functioning as a central hub in protein-protein interaction networks. In T cells, the dominant mechanism involves JAK/STAT pathway modulation, with adalimumab increasing STAT6 phosphorylation and restoring STAT4 activation to healthy levels, while disrupting Th1, Th17, and Th22 pathways in psoriasis patients. Adalimumab also affects the TNFα-TGFβ signaling axis differentially depending on disease context, effectively decreasing downstream inflammation in extended-to-be juvenile idiopathic arthritis synoviocytes but showing paradoxical increases in persistent disease...
Paper search
We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of Semantic Scholar and OpenAlex.
Characteristics of Included Studies
| Study | Full text retrieved? | Experimental context | Cell type/tissue | Disease model | Inflammatory stimulus |
|---|---|---|---|---|---|
| N. Mehta et al., 2018 | Yes | Randomized controlled trial | Patient samples | Psoriasis (moderate-to-severe) | Adalimumab (blocks TNF-α) |
| B. Grabarek et al., 2019 | No | Cell culture | Normal human dermal fibroblasts | Psoriasis | None mentioned |
| Paulina Buda et al., 2023 | Yes | Cell culture | Human keratinocytes (HaCaT) | Psoriasis | Lipopolysaccharide A (LPS) |
| Aleksandra Plata-Babula et al., 2025 | Yes | Cell culture | Immortalized keratinocytes (HaCaT) | Psoriasis | Lipopolysaccharide (LPS) |
...
Inflammatory Pathways Modulated by Adalimumab
NF-κB Signaling Pathway
The NF-κB pathway emerged as a central target of adalimumab modulation in keratinocytes. Adalimumab reversed LPS-induced upregulation of multiple NF-κB-associated genes, including IKBKB, IRAK1, TRAF2, MAP3K7, and TNFAIP3. STRING analysis identified IKBKB as a central hub in the protein-protein interaction network...
JAK/STAT Signaling Pathway
JAK/STAT pathway modulation occurred across multiple experimental contexts. In normal human dermal fibroblasts, adalimumab affected 18 of 37 JAK/STAT-associated mRNAs, with time-dependent changes in regulatory microRNAs...
TNFα-TGFβ Signaling Axis
In juvenile idiopathic arthritis synoviocytes, adalimumab demonstrated differential effects on persistent versus extended-to-be (ETB) fibroblast-like synoviocytes...
Notch-1 Signaling Pathway
In inflammatory bowel disease, adalimumab revealed a novel mechanism involving Notch-1 signaling...
Th1/Th17/Th22 Pathways
Clinical studies in psoriasis patients demonstrated that adalimumab disrupts multiple T helper cell pathways simultaneously...
Functional Outcomes
Adalimumab reduced key inflammatory markers across multiple studies. In psoriasis patients, treatment decreased serum CRP, IL-6, TNF, and glycoprotein acetylation (GlycA) at both 12 and 52 weeks...
Clinical and Phenotypic Improvements
Clinical improvements correlated with pathway modulation. In psoriasis, adalimumab improved skin disease and systemic inflammation markers...
Adverse Effects
Adalimumab demonstrated potential adverse effects on lipid metabolism...
Synthesis
The heterogeneous findings across studies can be reconciled by considering experimental context, disease model, and pathway-specific effects.
Context-Dependent Pathway Responses
The divergent effects of adalimumab on inflammatory mediators in different cell types reflect fundamental differences in cellular inflammatory programs...
Cell Type-Specific Mechanisms
The molecular mechanisms by which adalimumab modulates pathways vary substantially by cell type...
Temporal Dynamics of Response
Time-dependent effects reveal that pathway modulation by adalimumab follows distinct kinetics for different regulatory mechanisms...
Conclusion
Thus, our study indicates that adalimumab exerts the strongest modulating effect on mRNA and miRNA expression of JAK/STAT and IL-6-dependent IL-12/23 pathways.