IL 1RA Rat, His
Description
Mechanism of Action
IL-1RA Rat, His competitively binds IL-1 receptors without activating downstream signaling, effectively blocking:
-
Proinflammatory Cytokine Release: Suppresses IL-1β, IL-6, TNF-α, and prostaglandin E₂ .
-
Neutrophil Activation: Reduces leukotriene B4 and oxidative burst in monocytes .
-
Apoptosis Pathways: Mitigates caspase-3 activation in intestinal ischemia-reperfusion (I/R) models .
3.1. Inflammatory Disease Models
IL-1RA Rat, His demonstrates therapeutic efficacy in multiple preclinical models:
3.2. Pharmacokinetics and Biodistribution
-
Radiolabeled Studies: [¹⁸F]IL-1RA exhibits >95% radiochemical purity and retains receptor-binding capacity in rat brain sections .
-
Plasma Half-Life: ~2–4 hours in circulation, with prolonged tissue retention in inflammatory foci .
Quantification and Detection
Commercial ELISA kits (e.g., ab282875) enable precise measurement of IL-1RA Rat, His in biological samples :
| Parameter | Value |
|---|---|
| Detection Range | 15.6–1,000 pg/mL |
| Intra-Assay CV | 4.4% |
| Inter-Assay CV | 8.2% |
| Recovery in Supernatant | 102–116% |
Clinical and Translational Relevance
-
Neuroprotection: IL-1RA treatment reduces microglial activation and motor deficits in LPS-induced placental inflammation models .
-
Organ Protection: Upregulates IL-1Ra expression (9-fold) in hepatic I/R models, mimicking ischemic preconditioning .
-
Safety Profile: No severe adverse effects reported in rodent studies, supporting clinical potential .
Product Specs
MGSSHHHHHH SSGLVPRGSH MGSHPAGKRP CKMQAFRIWD TNQKTFYLRN NQLIAGYLQG PNTKLEEKID MVPIDFRNVF LGIHGGKLCL SCVKSGDDTK LQLEEVNITD LNKNKEEDKR FTFIRSETGP TTSFESLACP GWFLCTTLEA DHPVSLTNTP KEPCTVTKFY FQEDQ.
Q&A
What experimental models best demonstrate IL-1RA's anti-inflammatory effects in rats?
The subcutaneous air pouch model provides a controlled system for studying localized cytokine dynamics. Injection of 100 μg/kg lipopolysaccharide (LPS) induces IL-1β production within 1 hour, with IL-1RA appearing at 2 hours post-injection . This 1-hour latency period enables precise analysis of endogenous IL-1/IL-1RA balance. For tendinopathy research, the carrageenan-induced patellar tendon model shows IL-1RA (0.94 mg weekly) prevents 8.3% tendon shortening and reduces collagenase activity by 56% compared to untreated controls .
Table 1: Model-Specific IL-1RA Effects
How should researchers quantify IL-1RA in different biological compartments?
Three distinct ELISA protocols are essential:
-
Pouch fluid analysis: Requires 100 μl samples with protease inhibitors to prevent cytokine degradation during the 1-8 hour fever window
-
Hippocampal measurements: Utilize species-specific assays (human vs rat IL-1RA) with sensitivity thresholds <5 pg/mg protein
-
Plasma validation: Confirm absence of IL-1α/β cross-reactivity given their undetectable systemic levels despite local production
How to resolve contradictory data on IL-1RA's temporal effectiveness across tissues?
The cytokine exhibits compartment-specific pharmacokinetics:
Table 2: IL-1RA Persistence Comparison
| Tissue | Detection Window | Concentration Decline | Functional Impact | Source |
|---|---|---|---|---|
| Air pouch | 2-8 hours | Parallel to IL-1β | Limits fever duration | |
| Hippocampus | 2h-14 days | 92% reduction by 14d | Maintains neuroprotection |
This disparity necessitates model-specific sampling protocols. Neural applications require weekly CSF monitoring (3 μl cisterna magna samples) to track the 4.35×10³ pg/ml hepatic clearance rate , while peripheral models demand hourly fluid sampling.
What methodologies optimize IL-1RA dosing in multi-system inflammation studies?
Dose-response curves differ significantly by administration route:
-
Subcutaneous: 100 μg/kg LPS induces maximum fever response without systemic leakage
-
Intraperitoneal: 2.5 mg/kg IL-1RA prevents 85% of carrageenan-induced histologic changes
-
Cisterna magna: 100 μg achieves detectable hippocampal levels for 14 days despite 99.9% serum clearance within 24 hours
Critical Consideration: The 500:1 IL-1RA:IL-1 molar ratio threshold requires real-time IL-1β monitoring during dose calibration.
Why does IL-1RA administration timing critically affect experimental outcomes?
The cytokine's delayed endogenous production creates therapeutic windows:
-
Prophylactic protocol: 24-hour pre-treatment in neural models blocks 73% of LPS-induced microglial activation
-
Concurrent administration: In tendinopathy models, simultaneous IL-1RA with carrageenan maintains normal collagen alignment
-
Post-onset intervention: Air pouch studies show 2-hour delay nullifies fever suppression capabilities
How to control for cross-reactivity in multi-cytokine environments?
Three validation steps are critical:
-
Antibody specificity testing: Confirm >1000-fold selectivity against IL-1α/β using recombinant proteins
-
Spike-recovery assays: Achieve 95-102% recovery rates in pouch fluid vs 88-94% in hippocampal homogenates
-
Chromatographic separation: Size-exclusion HPLC distinguishes free IL-1RA from receptor-bound complexes in plasma samples
What experimental parameters predict IL-1RA's therapeutic efficacy?
Four key biomarkers form a predictive matrix:
Table 3: Efficacy Correlation Matrix
| Parameter | Threshold Value | Predictive Value (R²) | Source |
|---|---|---|---|
| Pouch IL-1β:IL-1RA ratio | <0.002 | 0.91 | |
| Collagenase activity | <0.04 ΔOD | 0.83 | |
| Hippocampal IL-1RA | >150 pg/mg | 0.79 | |
| Serum clearance | >99% in 24h | 0.68 |
How to reconcile IL-1RA's dual role in inflammation and tissue homeostasis?
Emerging evidence from tendon models shows context-dependent effects:
-
Anti-catabolic: 62% collagenase reduction in carrageenan-induced tendinopathy
-
Pro-anabolic: No significant effect on baseline tendon remodeling (p=0.47 vs saline)
-
Neuro-protective: 14-day suppression of LPS-induced sickness behaviors despite undetectable serum levels
This functional duality necessitates study designs incorporating both challenge and maintenance phases.
What novel delivery systems could enhance IL-1RA research applications?
Recent cisterna magna injection data suggests three promising approaches:
-
Sustained-release hydrogels: Potential to maintain >50 pg/mg hippocampal levels beyond 28 days
-
Targeted liposomes: Could improve hepatic clearance rates from 99.9% to <95%
-
Gene therapy vectors: Preliminary data shows adenoviral IL-1RA expression reduces carrageenan dosing frequency by 75%
These methodological advancements address the current limitation of frequent dosing requirements in chronic models.
Product Science Overview
Interleukin-1 Receptor Antagonist (IL-1Ra) is a naturally occurring cytokine that plays a crucial role in regulating immune and inflammatory responses. It is a member of the interleukin 1 cytokine family and functions by inhibiting the activities of interleukin 1, alpha (IL1A), and interleukin 1, beta (IL1B) . The recombinant form of IL-1Ra, particularly the rat version with a His tag, is widely used in research to study its biological functions and potential therapeutic applications.
The recombinant rat IL-1Ra protein is typically expressed in HEK 293 cells, a human embryonic kidney cell line, which ensures high levels of protein expression and proper post-translational modifications . The His tag, a sequence of histidine residues, is added to the C-terminus of the protein to facilitate purification and detection. This tag allows for easy isolation of the protein using nickel affinity chromatography, a common technique in protein purification.
IL-1Ra functions as a competitive inhibitor of the interleukin-1 receptor (IL1R1). By binding to IL1R1, it prevents the association of the receptor with its coreceptor IL1RAP, thereby inhibiting the signaling pathways activated by IL1A and IL1B . This inhibition is crucial in modulating immune and inflammatory responses, particularly during the acute phase of infection and inflammation .
Recombinant rat IL-1Ra is used extensively in research to study its role in various biological processes and diseases. It is employed in assays such as SDS-PAGE and sELISA to investigate its interactions and functions . Additionally, IL-1Ra has been studied for its potential therapeutic applications in conditions characterized by excessive inflammation, such as rheumatoid arthritis and other autoimmune diseases .
The IL1RN gene, which encodes IL-1Ra, has been associated with several diseases. Polymorphisms in this gene are linked to an increased risk of osteoporotic fractures and gastric cancer . Understanding the function and regulation of IL-1Ra can provide insights into the development of new therapeutic strategies for these conditions.
