Serum apolipoprotein A-1 is related to inammatory factors in the acute phase of gout

Serum concentrations of apoA-1, NLRP3 inammasome (cid:0) NACHT-LRR-PYD protein 3,NLRP3), interleukin-1 (IL-1) and interleukin-9 (IL-9) were detected. The correlation of serum apoA-1 concentration, gout related inammatory factors (NLRP3, IL-1 beta, IL-9) and other clinical and laboratory indicators analyzed. The serum apoA-1 concentration in the gout group was lower than that in the control group (P<0.05). With the increase of serum uric acid level, serum apoA-1 concentration decreased (cid:0) R 2 =-0.3160 (cid:0) P<0.05 (cid:0) . Multiple linear analyses were performed to increase blood glucose, blood lipid, liver and kidney, etc, and the correlation remained (cid:0) OR=-3.36 (cid:0) P<0.05 (cid:0) . With the increase of serum IL-1 beta concentration, serum apoA-1 concentration decreased (cid:0) R 2 =-0.3993 (cid:0) P<0.05 (cid:0) . Multiple linear analyses were performed to increase blood glucose, blood lipid, liver and kidney, etc., and the correlation remained (cid:0) OR=-2.95 (cid:0) P<0.05 (cid:0) .

Basic situation. There was no difference in gender and BMI among all subjects, and the gout group was younger. The blood pressure, blood creatinine, blood glucose and blood lipid of all the subjects were normal. Blood pressure, blood creatinine, and blood glucose increased in the gout group. High-density lipoprotein cholesterol decreased in gout group; blood uric acid increased in gout group: The subjects in the two groups (gout group and control group) were all male, and there was no statistically signi cant difference between the sexes (P > 0.05). There was no signi cant difference in body mass index (BMI) between the two groups of subjects (P > 0.05). There was no signi cant difference in age between the gout group (remission period) and the control group (P > 0.05).
The blood pressure, blood creatinine, blood sugar and blood lipids of the two groups of subjects were all within the normal range. Among them, the blood pressure, blood creatinine, and blood glucose levels of the gout group were higher than those of the control group, and the difference was statistically signi cant (P value < 0.05). The high-density lipoprotein cholesterol in the gout group (acute phase and remission phase) was lower than that in the control group, the difference was statistically signi cant (P value < 0.05). The blood uric acid in the gout group was higher than that in the control group, the difference was statistically signi cant (P < 0.05). (Table.1 diastolic blood pressure, Cr: creatinine, GLu: blood glucose, UA: uric acid, IL-1β: interleukin-1β, IL-9: interleukin-9, TG: triglycerides, TC: total cholesterol, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density lipoprotein cholesterol.

apoA-1 and in ammation index level
The plasma apoA-1 decreased in the gout group, and the plasma IL-1β, IL-9, NLRP3 increased the plasma apoA-1 in the gout group was lower than the control group, the difference was statistically signi cant (P < 0.05). The plasma IL-1β, IL-9 and NLRP3 in the gout group (acute phase and remission phase) were higher than the control group, the difference was statistically signi cant (P value < 0.05). (Table.1)

Discussion
With the improvement of living standards, the prevalence of gout has risen sharply in the past two decades, becoming an increasingly serious public health problem [5].Repeated attacks of acute gout affect people's health-related quality of life [6]. Chronic gout cause joint damage and dysfunction [7]. As a result, hospitalizations caused by gout continue to increase, further increasing the social and economic impact of the disease. Hyperuricemia is the biochemical basis for the occurrence of gout. Abnormal blood uric acid metabolism and blood lipid metabolism are inextricably linked [8,9]. Therefore, apoA-1 is selected as the core of the research. To explore the correlation with blood uric acid level and in ammation-related indexes of gout.
Apoprotein A-I (apoA-1), mainly synthesized by hepatocytes and intestinal cells, is the main component of high density lipoprotein (HDL) [2]. HDL has a versatile anti-atherosclerosis effect on the one hand, the second main feature is its anti-in ammatory properties [3,10]. HDL may be given an antiatherosclerotic and anti-in ammatory properties of apoA-1. The anti-in ammatory properties of HDL in experimental models in vitro and in vivo are consistent [11][12][13]. In the study of rheumatoid arthritis, the plasma apoA-1 and HDL levels of newly diagnosed rheumatoid arthritis patients were lower than those of normal people. In contrast, apoA-1 levels in the synovial uid of patients with rheumatoid arthritis are elevated. Although the level of apoA-1 in joint uid is only less than 1/10 of the plasma level, it indicates that apoA-1 in ltrates in the in ammatory joints of rheumatoid arthritis [14].In immune-related in ammation, immune in ammatory cells in ltrate the target tissue, resulting in tissue damage. In chronic in ammation, T lymphocytes are activated, thereby activating monocytes, and monocytes produce a large number of in ammatory factors. These in ammatory factors include Tumor Necrosis Factor-α (TNF-α) and IL-1β, which in turn triggers a Series cascade reaction. The imbalance of in ammatory factors and their inhibitors is one of the characteristics of chronic in ammation. Studies have con rmed that apoA-1 inhibits the activation of monocytes by T lymphocytes. Thereby inhibiting the production of TNF-α and IL-1β, apoA-1 interferes with the interaction of T lymphocytes and monocytes [15,16].
Gouty arthritis has the activation of NLRP3 in ammatory body, and the subsequent maturation and secretion of IL-1β [17,18]. IL-9 is produced by various immune cells, such as helper T cells, mast cells, eosinophils, and type 2 congenital lymphocytes, and depends on them to perform various functions. A large number of studies have con rmed the various in vivo functions of IL-9, including the promotion of allergic and immune diseases. This study found that plasma NLRP3, IL-1β, and IL-9 in the gout group were all elevated, which was consistent with previous studies [19,20]. This study con rmed that with the increase of blood uric acid level, IL-1β concentration increased, plasma apoA-1 concentration decreased. It suggests that apoA-1 may show anti-in ammatory activity by affecting in ammatory factors. The mechanism of action of apoA-1 has not been fully elucidated, and further research is to be done.

Declarations
Ethics approval and consent to participate The study was approved by the Ethics Committee of Beijing Luhe hospital, Capital Medical University (2020-LHKY-019-03). Figure 1 apoA-Iis associated with blood uric acid and IL-1β