58 5 ART for Anti-inflammation
relatively lower than CIA mice. The maximal NO level was detected in CIA mice
(40 mM) than in BIA-CIA mice (25 mM) or BIA mice (20 mM) during modeling.
These results clarified that CII (alloantigen) and live bacteria or dead bacteria in
CFA (xenoantigen) can more or less produce NO.
5.2.2.3 NO-Correlated Hypoxic Consequences Following Infection
or Immunization
To confirm the possibility of potent NO burst leading to hypoxia, we directly mon-
itored a fluctuation of SpO 2 in modeling mice with erythematous and edematous
paws. A dramatic decrease of SpO 2 was determined within the hind legs of CIA
mice, whereas only a slight decrease of SpO 2 was measured in those of BIA-CIA
and BIA mice. Interestingly, a lower SpO 2 was found to perfectly correlate with a
higher NO level and vice versa. For instance, 7 mM NO corresponds 80 % SpO 2
in control mice, while 17 mM NO accords 50 % SpO 2 in CIA mice. Control mice
have a lower NO level (7.14 mM) and a higher SpO 2 (83.5 %), but BIA mice have
a higher NO level (11.03 mM) and a lower SpO 2 (69.5 %) (Fig. 5.1).
To find out further evidence confirming NO-driven hypoxia, we evaluated
whether NO correlates with lactic acid (LA) in modeling mice. Consequently, a
higher NO level (10 μM) has relevance to a higher LA level (12 mM) in mice fed
with bacteria for 28 days or injected by CFA for two days. In control mice, both
NO and LA kept the stable levels. These results indicated that NO-driven hypoxia
might promote the anaerobic degradation of carbohydrates by glycolysis, leading
to the accumulation of LA in blood and tissues.
Fig. 5.1 Dynamic monitoring of NO production and comparative analysis of relationship
between NO and SpO 2 in BIA, CIA and BIA-CIA mice. a Time course detection of serum NO
levels in model mice. BIA bacteria-induced arthritis; CIA collagen-induced arthritis; NO nitric
oxide; SpO 2 saturation percentages of O 2. Sampling and detection were conducted every five
days and until 25 days during modeling. b Measurement of SpO 2 and NO in BIA, CIA, and BIA-
CIA mice. Sampling and detection were conducted after modeling for three days in CIA and
BIA-CIA mice or after modeling for 28 days in BIA mice. The singular asterisk (*) represents
statistically significant difference from the control (p < 0.05), and double asterisks (**) indicate
statistically very significant difference from the control (p < 0.01)