Parameter analysis of an ovalbumin combined with aluminum hydroxide adjuvant-induced allergic rhinitis model in BALB/c mice: a systematic review and meta-analysis
摘要
To systematically evaluate the key modeling parameters of an allergic rhinitis (AR) model induced by ovalbumin (OVA) combined with aluminum hydroxide [Al(OH)₃] adjuvant in BALB/c mice, and to compare the effects of different sensitization and challenge protocols on model induction, thereby providing a reference for model standardization.
MethodsA systematic search was conducted in PubMed, Embase, Web of Science and the Cochrane Library to identify studies using OVA combined with Al(OH)₃ to establish mouse models of AR. Data were extracted on animal strain, modeling protocols, and behavioral, immunological, and histopathological outcome measures. The model induction effects were evaluated using the standardized mean difference (SMD) and 95% confidence interval (95% CI). Subgroup analysis, meta-regression, sensitivity analysis, and the GRADE approach were performed to assess the robustness of the findings and the quality of evidence.
ResultsOVA combined with Al(OH)₃ effectively induced AR-related phenotypes in BALB/c mice, as evidenced by increased behavioral symptoms such as sneezing and nasal rubbing, accompanied by elevated OVA-specific IgE levels, increased expression of Th2-type inflammatory cytokines, and eosinophil infiltration in the nasal mucosa.Based on multiple outcome measures, three intraperitoneal sensitizations followed by intranasal OVA challenges for either 5 or 7 consecutive days appeared to achieve a relatively favorable model-induction effect. The effects of different OVA/Al(OH)₃ sensitization dose combinations were outcome-specific: 100 µg OVA plus 2 mg Al(OH)₃ showed a relatively large effect size for short-term sneezing responses; 50 µg OVA plus 1 mg Al(OH)₃ was more prominent in inducing eosinophil infiltration in the nasal mucosa; and 25 µg OVA plus 2 mg Al(OH)₃ exhibited a higher effect size for IL-5 levels in nasal lavage fluid. Regarding the intranasal challenge regimen, daily intranasal challenge with 400 µg OVA for either 5 or 7 consecutive days may be more favorable for inducing local Th2-type inflammatory responses in the nasal mucosa.Significant publication bias was observed for all major outcome measures, as indicated by Begg’s test (P < 0.001), suggesting a potential risk of overestimation of effect sizes. Nevertheless, the core conclusions remained robust after trim-and-fill correction. Some outcome measures exhibited substantial heterogeneity, which may be attributable to differences in modeling dose, administration frequency, challenge regimen, detection methods, and animal sources.
ConclusionIn BALB/c mice, OVA combined with Al(OH)₃ is capable of inducing an AR model. Based on the available evidence, three intraperitoneal sensitizations followed by intranasal OVA challenges for either 5 or 7 consecutive days may serve as a basic modeling regimen for establishing an OVA/alum-induced AR model. The sensitization dose should be selected according to the primary outcome of interest: 100 µg OVA plus 2 mg Al(OH)₃ may be preferentially considered when behavioral outcomes are the main focus, whereas 50 µg OVA plus 1 mg Al(OH)₃ may be prioritized when nasal mucosal eosinophil infiltration is the primary endpoint. However, these recommendations should be interpreted with caution. The relevant evidence was mainly derived from indirect comparisons across studies, and the certainty of evidence assessed using an adapted GRADE approach was generally very low across the primary outcomes, mainly because of risk of bias, inconsistency, imprecision, and publication bias. Therefore, the above regimens should be adjusted according to the study objective, primary endpoint, and expected model intensity, rather than being interpreted as universally optimal protocols applicable to all mouse strains or experimental conditions.